Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status
In the second week of December 2019, unknown viral infection was identified in a small local fish and wild animal market in Wuhan city, Hubei province in China (Lu et al., 2020). Since this time, the virus has rapidly spread across mainland China, and now has reached other countries (Li et al., 2020a; Chen et al., 2020a). In the early stages of this virus spread, several cases of pneumonia of unknown etiology were reported. Patients have been diagnosed with severe acute respiratory infection symptoms and others with rapidly developing acute respiratory distress syndrome, acute respiratory failure and other serious complications leading to death (Nijuan et al., 2013). The Chinese Center for Disease Control and Prevention (CCDC) identified this infection as a novel coronavirus infection on Jan 7, 2020 and on Feb 11, 2020, the WHO announced a new name for the epidemic disease as 2019-new coronavirus disease (2019-nCoV and now known as COVID-19) (Organization, W.H., 2020). Additionally, the International Committee on Taxonomy of Viruses named 2019-nCoV as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a major global health concern and the WHO declared the coronavirus outbreak a global pandemic on March 2020 (Whitworth, 2020). As of April 14, 2020, COVID-19 has affected more than 1,948,617 patients in 210 countries and territories around the world and two international conveyances and left around 121,846 deaths worldwide.
Coronaviruses are belonging to the family Coronaviridae (order Nidovirales) and include viruses with a single-strand, positive-sense RNA genome approximately 26–32 kilobases in size (Weiss and Navas-Martin, 2005). The Coronaviridae family contains four genera to include Alpha-coronavirus (alphaCoV), Beta-coronavirus (betaCoV), Delta-coronavirus (deltaCoV) and Gamma-coronavirus (gammaCoV). Bats and rodents are thought to be the reservoir for alphaCoV and betaCoV. Currently, it is less clear which animals serve as the reservoir for deltaCoV and gammaCoV.
Coronaviruses are belonging to the family Coronaviridae (order Nidovirales) and include viruses with a single-strand, positive-sense RNA genome approximately 26–32 kilobases in size (Weiss and Navas-Martin, 2005). The Coronaviridae family contains four genera to include Alpha-coronavirus (alphaCoV), Beta-coronavirus (betaCoV), Delta-coronavirus (deltaCoV) and Gamma-coronavirus (gammaCoV). Bats and rodents are thought to be the reservoir for alphaCoV and betaCoV. Currently, it is less clear which animals serve as the reservoir for deltaCoV and gammaCoV.
These viruses typically affect the respiratory tracts of birds and mammals including humans. In general, the reservoir of these viruses is in animals that infrequent spillover into humans, with intermediate host species likely filling the gap. Among humans, CoVs mostly cause insignificant respiratory infections to include those detected in the common cold. Nevertheless, some recent CoVs can cause more serious diseases, including severe acute respiratory syndrome (SARS-CoV) and Middle East respiratory syndrome (MERS-CoV) (Zumla et al., 2016; Su et al., 2016). SARS-CoV and MERS-CoV are caused by zoonotic coronaviruses that belong to the betaCoV genus. In 2003, an outbreak of SARS started in China and spread to other countries before ending in 2004 (Falsey and Walsh, 2003). A total of 8098 cases in 37 countries/regions had probable SARS diagnoses globally resulting in 775 deaths (case-fatality rate: 10–12%) with most of these cases of infection and deaths occurring in mainland China and Hong Kong (Christian et al., 2004). In contrast, a total of 1621 cases of MERS have been reported resulting in 584 deaths (case-fatality rate: 36%). The initial known case of MERS was in a 60-year-old patient who died from a severe respiratory illness in Jeddah, Saudi Arabia, in 2012. MERS still sporadically manifests in several different countries (Raj et al., 2014). Upon infection with SARS-CoV-2, the virus binds to a host cell's angiotensin-converting enzyme 2 (ACE2) receptors. ACE2 is commonly expressed on the epithelial cells of alveoli, trachea, bronchi, and bronchial serous glands of the respiratory tract (Liu et al., 2011). The virus enters and replicates in these cells. The new developed virions are then released and infect new target cells.
**********
Origin and transmission
Although health officials are still tracing the exact source of the 2019 novel coronavirus, early hypotheses thought it may be linked to the Huanan seafood wholesale market in Wuhan city where live animals are sold, to include snakes, marmots, birds, frogs and hedgehogs (Zhang et al., n.d.). Some people who visited the market developed viral pneumonia caused by the new coronavirus. This fact suggested that animals initially transmitted the virus to humans. However, people with a more recent diagnosis had no connections with or exposure to the market, confirming that humans can pass the virus to each other. The 2019 novel coronavirus is a zoonotic virus, meaning the first patients who were infected acquired these viruses directly from animals. Some studies have shown that the bat is the possible species of origin of the 2019 novel coronavirus (SARS-CoV-2) because SARS-CoV-2 shows 96% whole-genome identity with a bat CoV (BatCoV RaTG13) from Rhinolophus affinis (Zhou et al., 2020). Nevertheless, SARS-CoV and MERS-CoV are generally transmitted into intermediate hosts to include masked palm civets and camels, respectively, before jumping to humans (Cui et al., 2019). A number of scientists pointed out that as a result of the similarity of this new virus with SARS-CoV and MERS-CoV, SARS-CoV-2 has probably moved from un unknown intermediate host to humans or directly to humans (Zhou et al., 2020).
As of Jan 17, 2020, a Chinese team conducted an analysis and compared the genetic sequences of 2019-nCoV and all other known coronaviruses. They proposed that 2019-nCoV has most similar codon usage bias with snakes (Ji et al., 2020). Snakes often hunt bats in the wild. Reports indicate that snakes were sold in the local seafood market in Wuhan, raising the possibility that the 2019-nCoV might have jumped from the host species, bats, to snakes and then to humans at the beginning of this coronavirus outbreak. However, how the virus could adapt to both cold-blooded and warm-blooded hosts remains a mystery (Ji et al., 2020). Moreover, there is no reliable evidence that coronaviruses live in hosts other than mammals and birds (Bassetti et al., 2020). Therefore, there is probably a mammal intermediate host for 2019-nCoV (Zhang et al., 2020a). On March 19, 2020, a published article showed that the Pangolin-CoV genome exhibited 91% and 90.6% nucleotide identity with SARS-CoV-2 and BatCoV RaTG13, respectively. This study provides the first report of a potential closely related kin (Pangolin-CoV) of SARS-CoV-2, which was discovered from dead Malayan pangolins (Manis javanica), identifying the pangolin a possible intermediate host of the 2019-nCoV (Zhang et al., n.d.; Zhang et al., 2020a). Although current understanding mostly points to the pangolin as the most likely intermediate host for the new coronavirus, it is possible other animals as also may be intermediate hosts. Generally, coronaviruses are well-known to have many intermediate animal hosts. In 2003, studies showed that the palm civet (Paguma larvata) is the major intermediate host of SARS-CoV, but other reports also suggest that the raccoon dog
Although health officials are still tracing the exact source of the 2019 novel coronavirus, early hypotheses thought it may be linked to the Huanan seafood wholesale market in Wuhan city where live animals are sold, to include snakes, marmots, birds, frogs and hedgehogs (Zhang et al., n.d.). Some people who visited the market developed viral pneumonia caused by the new coronavirus. This fact suggested that animals initially transmitted the virus to humans. However, people with a more recent diagnosis had no connections with or exposure to the market, confirming that humans can pass the virus to each other. The 2019 novel coronavirus is a zoonotic virus, meaning the first patients who were infected acquired these viruses directly from animals. Some studies have shown that the bat is the possible species of origin of the 2019 novel coronavirus (SARS-CoV-2) because SARS-CoV-2 shows 96% whole-genome identity with a bat CoV (BatCoV RaTG13) from Rhinolophus affinis (Zhou et al., 2020). Nevertheless, SARS-CoV and MERS-CoV are generally transmitted into intermediate hosts to include masked palm civets and camels, respectively, before jumping to humans (Cui et al., 2019). A number of scientists pointed out that as a result of the similarity of this new virus with SARS-CoV and MERS-CoV, SARS-CoV-2 has probably moved from un unknown intermediate host to humans or directly to humans (Zhou et al., 2020).
As of Jan 17, 2020, a Chinese team conducted an analysis and compared the genetic sequences of 2019-nCoV and all other known coronaviruses. They proposed that 2019-nCoV has most similar codon usage bias with snakes (Ji et al., 2020). Snakes often hunt bats in the wild. Reports indicate that snakes were sold in the local seafood market in Wuhan, raising the possibility that the 2019-nCoV might have jumped from the host species, bats, to snakes and then to humans at the beginning of this coronavirus outbreak. However, how the virus could adapt to both cold-blooded and warm-blooded hosts remains a mystery (Ji et al., 2020). Moreover, there is no reliable evidence that coronaviruses live in hosts other than mammals and birds (Bassetti et al., 2020). Therefore, there is probably a mammal intermediate host for 2019-nCoV (Zhang et al., 2020a). On March 19, 2020, a published article showed that the Pangolin-CoV genome exhibited 91% and 90.6% nucleotide identity with SARS-CoV-2 and BatCoV RaTG13, respectively. This study provides the first report of a potential closely related kin (Pangolin-CoV) of SARS-CoV-2, which was discovered from dead Malayan pangolins (Manis javanica), identifying the pangolin a possible intermediate host of the 2019-nCoV (Zhang et al., n.d.; Zhang et al., 2020a). Although current understanding mostly points to the pangolin as the most likely intermediate host for the new coronavirus, it is possible other animals as also may be intermediate hosts. Generally, coronaviruses are well-known to have many intermediate animal hosts. In 2003, studies showed that the palm civet (Paguma larvata) is the major intermediate host of SARS-CoV, but other reports also suggest that the raccoon dog
With increasing cases of infection with 2019-nCoV, several studies have proposed that human-to-human transmission is a probable route for the COVID-19 outbreak. These studies are supported by the number of infection cases that happened within families and among people who did not visit the local animal market in Wuhan (Carlos et al., 2020). The virus mainly spreads from one person to another, usually through close contact or through respiratory drops produced when the infected person coughs or sneezes, which is why it is important to keep more than two meters (6 ft. 7 in) away from a sick person (Li et al., 2020a). However, it is not just sneezing or coughing that is the source of transmission of the coronavirus infection. There are other ways to transmit the virus to include spreading from one person to another through surfaces that have been touched by the infected person, especially after studies have demonstrated that the virus remains alive on surfaces for possibly up to 9 days (Phan et al., 2020; Riou and Althaus, 2020). People can then develop COVID-19 disease when they come into contact with these objects or surfaces and then touch their eyes, nose or mouth. Moreover, studies to date indicate that 2019-nCoV is transmitted primarily through contact with respiratory droplets rather than through the air. A person who suffers from a mild cough and does not feel ill can infect COVID-19. There is another way in which coronavirus can spread among people through feces transmission, but this route of infection is limited. According to recent research from the CCDC, the virus may be present in feces in some infected cases, though; its spread through this pathway is not a major feature of the outbreak (Xiao et al., 2020; Gu et al., 2020). Nevertheless, given the risks involved, this is another reason to maintain good hygiene after using the toilet and before eating.
At this time, very little is known regarding the effect of 2019-nCoV on pregnant women and infants and there are currently no special recommendations for pregnant women regarding the disease (Schwartz and Graham, 2020). The CDC does not have any evidence indicating the possibility of negative pregnancy outcomes for pregnant women with COVID-19, although two of the other coronaviruses SARS-CoV and MERS-CoV have been associated with more severe diseases and greater mortality in pregnant women (Maxwell et al., 2017; Assiri et al., 2016). A report by the China-WHO Joint Mission published in mid-February 2020 showed that in 147 pregnant women infected with 2019-nCoV, 8% of the cases were considered severe and 1% were critical (Chen et al., 2020b). These numbers appear to be comparable with non-pregnant infected cases. Another article published on March 7, 2020, showed clinical data from nine pregnant women in China with confirmed COVID-19 pneumonia. The physical appearance of these patients with COVID-19 infection during pregnancy were similar to those of non-pregnant adults with COVID-19. None of the nine patients developed severe pneumonia or died (Chen et al., 2020b). In the limited number of available cases in which newborns were born from mothers with 2019-nCoV, no children were infected with the virus. In addition, the virus did not appear in samples of amniotic fluid surrounding the fetus while in uterus. Furthermore, 2019-nCoV does not pass through the placenta (Schwartz and Graham, 2020). No scientific studies have been done on the 2019-nCoV and breast milk. A newborn in London has tested positive for 2019-nCoV, just minutes after being born to a mother who was also infected with the virus, according to news reports. This is not the first case because the Chinese authorities confirmed that an infant in Wuhan, China, had tested positive for the 2019-nCoV thirty hrs after being born; the baby's mother was a COVID-19 patient. Reliable data is needed to understand how these infants are infected, and whether transmission of the virus to the fetus occurs pregnancy or sometime during or after delivery.
At this time, very little is known regarding the effect of 2019-nCoV on pregnant women and infants and there are currently no special recommendations for pregnant women regarding the disease (Schwartz and Graham, 2020). The CDC does not have any evidence indicating the possibility of negative pregnancy outcomes for pregnant women with COVID-19, although two of the other coronaviruses SARS-CoV and MERS-CoV have been associated with more severe diseases and greater mortality in pregnant women (Maxwell et al., 2017; Assiri et al., 2016). A report by the China-WHO Joint Mission published in mid-February 2020 showed that in 147 pregnant women infected with 2019-nCoV, 8% of the cases were considered severe and 1% were critical (Chen et al., 2020b). These numbers appear to be comparable with non-pregnant infected cases. Another article published on March 7, 2020, showed clinical data from nine pregnant women in China with confirmed COVID-19 pneumonia. The physical appearance of these patients with COVID-19 infection during pregnancy were similar to those of non-pregnant adults with COVID-19. None of the nine patients developed severe pneumonia or died (Chen et al., 2020b). In the limited number of available cases in which newborns were born from mothers with 2019-nCoV, no children were infected with the virus. In addition, the virus did not appear in samples of amniotic fluid surrounding the fetus while in uterus. Furthermore, 2019-nCoV does not pass through the placenta (Schwartz and Graham, 2020). No scientific studies have been done on the 2019-nCoV and breast milk. A newborn in London has tested positive for 2019-nCoV, just minutes after being born to a mother who was also infected with the virus, according to news reports. This is not the first case because the Chinese authorities confirmed that an infant in Wuhan, China, had tested positive for the 2019-nCoV thirty hrs after being born; the baby's mother was a COVID-19 patient. Reliable data is needed to understand how these infants are infected, and whether transmission of the virus to the fetus occurs pregnancy or sometime during or after delivery.
************
Symptoms
If someone is infected with the 19-nCoV, the first symptoms usually appear after five to six days, according to the WHO reports (Li et al., 2020a). However, there are individual cases, in which the incubation period of the virus can last for up to 40 days with a median incubation period of 14 days (Wang et al., 2020a). The incubation period for severe cases may be different compared to mild cases and depend on the age of the patient and their immune response. This period tended to be shorter among patients >70 years (11.5 days) than those aged <70 years (20 days) (Wang et al., 2020a). The symptoms of COVID-19 are usually like a normal cold and influenza and do not become severe. However, it is different for people suffering from underlying diseases such as diabetes, heart, lung and other diseases. In this case, the disease can take on critical forms that sometimes lead to death. Some people have no symptoms (mild pneumonia). The most common symptoms of COVID-19 according to a recent WHO report that was done on more than 70,000 cases in China are the following: fever (in 88% of cases), dry cough and sore throat (68%), fatigue (38%) and diarrhea (4%), which were similar to SARS-CoV and MERS-CoV (Yang et al., 2020a; Wang et al., n.d.). Furthermore, severe shortness of breath occurred in nearly 20% of cases and around 13% had a sore throat or severe headache. Generally, 19-nCoV is a member of coronaviruses family that usually attack the respiratory system. Some patients are disposed to various complications to include acute respiratory distress syndrome, acute heart injury and secondary infection with bacteria
If someone is infected with the 19-nCoV, the first symptoms usually appear after five to six days, according to the WHO reports (Li et al., 2020a). However, there are individual cases, in which the incubation period of the virus can last for up to 40 days with a median incubation period of 14 days (Wang et al., 2020a). The incubation period for severe cases may be different compared to mild cases and depend on the age of the patient and their immune response. This period tended to be shorter among patients >70 years (11.5 days) than those aged <70 years (20 days) (Wang et al., 2020a). The symptoms of COVID-19 are usually like a normal cold and influenza and do not become severe. However, it is different for people suffering from underlying diseases such as diabetes, heart, lung and other diseases. In this case, the disease can take on critical forms that sometimes lead to death. Some people have no symptoms (mild pneumonia). The most common symptoms of COVID-19 according to a recent WHO report that was done on more than 70,000 cases in China are the following: fever (in 88% of cases), dry cough and sore throat (68%), fatigue (38%) and diarrhea (4%), which were similar to SARS-CoV and MERS-CoV (Yang et al., 2020a; Wang et al., n.d.). Furthermore, severe shortness of breath occurred in nearly 20% of cases and around 13% had a sore throat or severe headache. Generally, 19-nCoV is a member of coronaviruses family that usually attack the respiratory system. Some patients are disposed to various complications to include acute respiratory distress syndrome, acute heart injury and secondary infection with bacteria
Epidemiology
The rapidly spreading 2019-nCoV outbreak continued to upend life around the world as more countries tighten quarantine measures. On March 11, the COVID-19 outbreak was characterized as a pandemic by the WHO. The disease is still spreading around the world and the viral infection has already reached small islands and African countries. In December 8, 2019, SARS-CoV-2 was first reported in Wuhan, Hubei province and spread to the rest of China (Cascella et al., 2020). As of April 14, 2020, the number of COVID-19-diagnosed patients increased to 1,948,617 cases in 210 countries and territories around the world and two international conveyances. So far, the number of those recovering has reached about 460,541 while 121,846 have died from the disease (case-fatality rate: 6.25%) (Fig. 5 ). Although, COVID-19 has killed more people than other coronaviruses, the case fatality rate of SARS-CoV-2 is less than that of SARS-CoV and MERS-CoV, which are 10–12% and 36%, respectivel
The rapidly spreading 2019-nCoV outbreak continued to upend life around the world as more countries tighten quarantine measures. On March 11, the COVID-19 outbreak was characterized as a pandemic by the WHO. The disease is still spreading around the world and the viral infection has already reached small islands and African countries. In December 8, 2019, SARS-CoV-2 was first reported in Wuhan, Hubei province and spread to the rest of China (Cascella et al., 2020). As of April 14, 2020, the number of COVID-19-diagnosed patients increased to 1,948,617 cases in 210 countries and territories around the world and two international conveyances. So far, the number of those recovering has reached about 460,541 while 121,846 have died from the disease (case-fatality rate: 6.25%) (Fig. 5 ). Although, COVID-19 has killed more people than other coronaviruses, the case fatality rate of SARS-CoV-2 is less than that of SARS-CoV and MERS-CoV, which are 10–12% and 36%, respectivel
***************
Therapeutics and available treatment options
Unfortunately, no medicine or anti-virus vaccine has yet been officially approved to treat COVID-19-associated pathologies. At present clinical management includes infection prevention, control measures and supportive care including supplementary oxygen and mechanical ventilation when indicated. While many countries are working toward a vaccine against SARS-CoV-2, it is almost certain that there will be no vaccine available before the end of this year. Therefore, pressure has built to find another drug to effectively counter the virus. This effort has mostly focused on repurposing existing medicines. Health officials from the WHO have noted many drugs that demonstrated efficacy in treating the 2019-nCoV infection. The main treatment so far for this virus is using antivirals, which weaken the ability of viruses to enter cells and prevent them from multiplying or moving from infected cells to others. Antibiotics have no role in treating COVID-19 patients, but they can be used in the case of a secondary bacterial infection.
Since the disease first appeared in December 2019 in China, this country has begun to test the effectiveness of different types of drugs used previously to treat other diseases to include malaria and HIV drugs, antivirals, blood plasma derivatives and arthritis drugs (Li and De Clercq, 2020). China has relied on the use of the anti-viral drug Favilavir to treat the symptoms of COVID-19. This medication was initially developed by Toyama Chemical to treat nose and throat infections (Li et al., n.d.). Although the results of the study have not yet been published, it is assumed that the drug has proven effective in treating symptoms of COVID-19 in a clinical trial of more than 70 patients with minimal side effects. Favilavir is an antiviral drug that was approved in Japan in 2014 to treat influenza. It currently also has been approved for treating COVID-19 in these countries (Elfiky, 2020). Favilavir is not currently approved by the U.S. Food and Drug Administration (FDA) (Li and De Clercq, 2020). Another anti-virus drug, Remdesivir showed efficacy by resisting two viruses similar to Covid-19, SARS-CoV and MERS-CoV, in animals (Wang et al., 2020b). Remdesivir (GS-5734) is a broad-based antiviral drug originally designed to target Ebola and was developed by Gilead Sciences. It inhibits viral replication through premature termination of RNA transcription, which disrupts the virus's ability to reproduce (Li et al., n.d.). China announced that clinical trials of remdesiver, have officially started in a number of hospitals in Wuhan to test its efficacy against COVID-19. Moreover, one clinical trial has also been approved by the FDA in the United States. On January 19, 2020, remdesiver was given to a 35-year-old man in Washington State. He has recovered from COVID-19 (Holshue et al., 2020). However, the efficacy and safety of remdesiver in patients with 2019-nCoV infection still need to be further confirmed by clinical studies.
Chloroquine and Hydroxychloroquine are drugs used to treat malaria, as well as chemoprophylaxis; and certain inflammatory conditions to include rheumatoid arthritis, lupus and the blood disorder porphyria cutanea tarda, respectively. They have been approved by the FDA to be tested against COVID-19 (Dong et al., 2020a). Researchers have found that both drugs have in vitro activity against SARS-CoV and SARS-CoV-2, with hydroxychloroquine having relatively higher potency against SARS-CoV-2. Based on these results, chloroquine and hydroxychloroquine are currently recommended for treatment of hospitalized COVID-19 patients in several countries, including in the U S. A Chinese study showed that when chloroquine was tested on more than 100 patients, it had superior results compared to a control drug inhibiting the exacerbation of pneumonia, improving lung-imaging findings, promoting a virus negative conversion and shortening the disease course (Zhonghua Jie He He Hu Xi Za Zhi, 2020; Gao et al., 2020). However, both chloroquine and hydroxychloroquine are never used to prevent COVID-19 because there are frequent side effects associated with their uses, such as worsening vision, nausea, digestive disorders and more severe cases can lead to heart failure.. A man in Arizona died and his wife was in critical condition after taking chloroquine prophylactically to prevent SARS-CoV-2 infection.
In 2003, protease inhibitors lopinavir/ritonavir (anti-retroviral drugs) showed activity against SARS-CoV and was associated with improvement in some patients (Chu et al., 2004; Chan et al., 2003). Lopinavir/ritonavir are sold under the name Kaletra by AbbVie and are designed to treat HIV (AIDS). To evaluate the efficacy of lopinavir/ritonavir for SARS-CoV-2 infection, 99 patients with positive infections were treated with lopinavir/ritonavir. No benefit was observed with lopinavir/ritonavir treatment compare to standard care (Cao et al., 2020). However, in South Korea, a 54-year-old man was given a combination of these two medications and had a significant and substantial decrease in the levels of the β-coronavirus (Lim et al., 2020). According to the WHO, there may be benefits to using lopinavir/ritonavir with other drugs such as interferon-β, oseltamivir or ribavirin (Elfiky, 2020).
Several studies have also exposed some other drugs may have probable efficiency in treatment of COVID-19 patients. In China, the use of Tocilizumab for the treatment of severe complications related to SARS-CoV-2 has been approved. Tocilizumab, marketed as Actemra, has been used to treat patients with moderate to severe rheumatoid arthritis to lower inflammation. An initial clinical trial in China used tocilizumab on 20 acute COVID-19 patients. Nineteen patients (95%) were cured and discharged from hospital within two weeks (Zhang et al., 2020b). The FDA has officially approved a phase 3 trial of Actemra in severe COVID-19 patients. Darunavir is another anti-retroviral HIV-1 protease inhibitor. In vitro study was done in February 2020, by Chinese researchers has showen darunavir significantly inhibited SARS-CoV-2 replication and its inhibition efficacy was more than that in the untreated group by 280-fold (Dong et al., 2020b). An anti-parasitic drug called ivermectin has been shown to be effective against the SARS-CoV-2 virus in an in-vitro study by researchers at Monash University in Melbourne, Australia (Caly et al., 2020). Further clinical trials need to be completed to confirm the effectiveness of the drug in humans with COVID-19.
Since the disease first appeared in December 2019 in China, this country has begun to test the effectiveness of different types of drugs used previously to treat other diseases to include malaria and HIV drugs, antivirals, blood plasma derivatives and arthritis drugs (Li and De Clercq, 2020). China has relied on the use of the anti-viral drug Favilavir to treat the symptoms of COVID-19. This medication was initially developed by Toyama Chemical to treat nose and throat infections (Li et al., n.d.). Although the results of the study have not yet been published, it is assumed that the drug has proven effective in treating symptoms of COVID-19 in a clinical trial of more than 70 patients with minimal side effects. Favilavir is an antiviral drug that was approved in Japan in 2014 to treat influenza. It currently also has been approved for treating COVID-19 in these countries (Elfiky, 2020). Favilavir is not currently approved by the U.S. Food and Drug Administration (FDA) (Li and De Clercq, 2020). Another anti-virus drug, Remdesivir showed efficacy by resisting two viruses similar to Covid-19, SARS-CoV and MERS-CoV, in animals (Wang et al., 2020b). Remdesivir (GS-5734) is a broad-based antiviral drug originally designed to target Ebola and was developed by Gilead Sciences. It inhibits viral replication through premature termination of RNA transcription, which disrupts the virus's ability to reproduce (Li et al., n.d.). China announced that clinical trials of remdesiver, have officially started in a number of hospitals in Wuhan to test its efficacy against COVID-19. Moreover, one clinical trial has also been approved by the FDA in the United States. On January 19, 2020, remdesiver was given to a 35-year-old man in Washington State. He has recovered from COVID-19 (Holshue et al., 2020). However, the efficacy and safety of remdesiver in patients with 2019-nCoV infection still need to be further confirmed by clinical studies.
Chloroquine and Hydroxychloroquine are drugs used to treat malaria, as well as chemoprophylaxis; and certain inflammatory conditions to include rheumatoid arthritis, lupus and the blood disorder porphyria cutanea tarda, respectively. They have been approved by the FDA to be tested against COVID-19 (Dong et al., 2020a). Researchers have found that both drugs have in vitro activity against SARS-CoV and SARS-CoV-2, with hydroxychloroquine having relatively higher potency against SARS-CoV-2. Based on these results, chloroquine and hydroxychloroquine are currently recommended for treatment of hospitalized COVID-19 patients in several countries, including in the U S. A Chinese study showed that when chloroquine was tested on more than 100 patients, it had superior results compared to a control drug inhibiting the exacerbation of pneumonia, improving lung-imaging findings, promoting a virus negative conversion and shortening the disease course (Zhonghua Jie He He Hu Xi Za Zhi, 2020; Gao et al., 2020). However, both chloroquine and hydroxychloroquine are never used to prevent COVID-19 because there are frequent side effects associated with their uses, such as worsening vision, nausea, digestive disorders and more severe cases can lead to heart failure.. A man in Arizona died and his wife was in critical condition after taking chloroquine prophylactically to prevent SARS-CoV-2 infection.
In 2003, protease inhibitors lopinavir/ritonavir (anti-retroviral drugs) showed activity against SARS-CoV and was associated with improvement in some patients (Chu et al., 2004; Chan et al., 2003). Lopinavir/ritonavir are sold under the name Kaletra by AbbVie and are designed to treat HIV (AIDS). To evaluate the efficacy of lopinavir/ritonavir for SARS-CoV-2 infection, 99 patients with positive infections were treated with lopinavir/ritonavir. No benefit was observed with lopinavir/ritonavir treatment compare to standard care (Cao et al., 2020). However, in South Korea, a 54-year-old man was given a combination of these two medications and had a significant and substantial decrease in the levels of the β-coronavirus (Lim et al., 2020). According to the WHO, there may be benefits to using lopinavir/ritonavir with other drugs such as interferon-β, oseltamivir or ribavirin (Elfiky, 2020).
Several studies have also exposed some other drugs may have probable efficiency in treatment of COVID-19 patients. In China, the use of Tocilizumab for the treatment of severe complications related to SARS-CoV-2 has been approved. Tocilizumab, marketed as Actemra, has been used to treat patients with moderate to severe rheumatoid arthritis to lower inflammation. An initial clinical trial in China used tocilizumab on 20 acute COVID-19 patients. Nineteen patients (95%) were cured and discharged from hospital within two weeks (Zhang et al., 2020b). The FDA has officially approved a phase 3 trial of Actemra in severe COVID-19 patients. Darunavir is another anti-retroviral HIV-1 protease inhibitor. In vitro study was done in February 2020, by Chinese researchers has showen darunavir significantly inhibited SARS-CoV-2 replication and its inhibition efficacy was more than that in the untreated group by 280-fold (Dong et al., 2020b). An anti-parasitic drug called ivermectin has been shown to be effective against the SARS-CoV-2 virus in an in-vitro study by researchers at Monash University in Melbourne, Australia (Caly et al., 2020). Further clinical trials need to be completed to confirm the effectiveness of the drug in humans with COVID-19.
**********
Guidelines to prevent the spread of SARS-CoV-2 infection
Vaccine development takes time. Thus, for now it remains extremely important to follow guidance on social separation, frequent hand washing and disinfecting your homes and workplaces (Xiao et al., n.d.). Several reports show that SARS-CoV-2 may spread more easily and cause life-threatening illness compared to other CoV viruses. Like other coronaviruses, it can survive in the air for up to 3 h and may stay on plastic for 72 h, 48 h on stainless steel, 24 h on cardboard and 4 h on copper (van Doremalen et al., 2020). However, SARS-CoV-2 multiplies fastest in the body even when an infected person does not show symptoms, and can be passed to other. The Prophet of Islam Mohamed (peace and blessings of Allah be upon him) recommended hygiene and quarantine during a pandemic, more than 1440 years ago. Hadiths of the Prophet (Sayings and Teachings) in this context, one of which is: If you heard about plague in a land, do not enter it, and if it occurred in a land while you are there, do not leave it. The WHO and other organizations have issued some basic guidelines to prevent COVID-19 including (i) washing your hands frequently and carefully, especially after contact with infected people or their environment; (ii) avoid touching your face including mouth, nose and eyes; (iii) cover your mouth and nose when coughing and sneezing; (iv) take social distancing seriously by keeping a distance of 6 ft from other people; and (v) self-quarantine if sick and wear a mask when you need medical care (Jin et al., 2020; Wang et al., 2020c). Furthermore, the WHO announced a document regarding the laboratory biosafety guidance related to the 2019-nCoV. Healthcare providers and researchers must wear FFP3 or N95 masks and other protective gear when around COVID-19 patients (Wang et al., 2020c). For healthy people wearing a mask may not be the best way to prevent getting an infection. 2019-nCoV may likely be susceptible to disinfectants with proven activity against enveloped viruses, including bleach (sodium hypochlorite), 70% ethanol, 0.5% hydrogen peroxide, quaternary ammonium compounds and phenolic compounds, if used according to manufacturer's recommendations. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate can be less effective
Vaccine development takes time. Thus, for now it remains extremely important to follow guidance on social separation, frequent hand washing and disinfecting your homes and workplaces (Xiao et al., n.d.). Several reports show that SARS-CoV-2 may spread more easily and cause life-threatening illness compared to other CoV viruses. Like other coronaviruses, it can survive in the air for up to 3 h and may stay on plastic for 72 h, 48 h on stainless steel, 24 h on cardboard and 4 h on copper (van Doremalen et al., 2020). However, SARS-CoV-2 multiplies fastest in the body even when an infected person does not show symptoms, and can be passed to other. The Prophet of Islam Mohamed (peace and blessings of Allah be upon him) recommended hygiene and quarantine during a pandemic, more than 1440 years ago. Hadiths of the Prophet (Sayings and Teachings) in this context, one of which is: If you heard about plague in a land, do not enter it, and if it occurred in a land while you are there, do not leave it. The WHO and other organizations have issued some basic guidelines to prevent COVID-19 including (i) washing your hands frequently and carefully, especially after contact with infected people or their environment; (ii) avoid touching your face including mouth, nose and eyes; (iii) cover your mouth and nose when coughing and sneezing; (iv) take social distancing seriously by keeping a distance of 6 ft from other people; and (v) self-quarantine if sick and wear a mask when you need medical care (Jin et al., 2020; Wang et al., 2020c). Furthermore, the WHO announced a document regarding the laboratory biosafety guidance related to the 2019-nCoV. Healthcare providers and researchers must wear FFP3 or N95 masks and other protective gear when around COVID-19 patients (Wang et al., 2020c). For healthy people wearing a mask may not be the best way to prevent getting an infection. 2019-nCoV may likely be susceptible to disinfectants with proven activity against enveloped viruses, including bleach (sodium hypochlorite), 70% ethanol, 0.5% hydrogen peroxide, quaternary ammonium compounds and phenolic compounds, if used according to manufacturer's recommendations. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate can be less effective
 - an update on the status){kind=link}
0 Comments