PROFILING THE CORONA VIRUS
Nahandoo Ichoron and John O. Igoli
The world was completely unprepared for what began in Wuhan, China in December 2019 and would spread like wild fire to become a pandemic. An elderly couple checked in with symptoms of pneumonia at Hubei Provincial Hospital of Integrated Chinese and Western Medicine in Wuhan, where Dr. Zhang Jixian is director of respiratory and critical care medicine. What alarmed the doctor was the similarity of the CT Scan images of their throat to those of SARS patients she had treated in 2003. Dr. Li Wenliang, an ophthalmologist at Wuhan Central Hospital had also seen similar cases1. As days passed, more patients checked in with similar symptoms across hospitals in Wuhan and it began to spread to other cities in China. This strange disease was later confirmed to be caused by a strain of corona virus not previously identified in humans. Corona viruses are usually found in bats and they cause a wide range of respiratory system diseases such as flu, common cold, Middle East Respiratory Syndrome (MERS) caused by MERS Corona Virus (MERS-CoV)2 and Severe Acute Respiratory Syndrome (SARS), caused by SARS Corona Virus (SARS-CoV)3. The new corona virus of 2019 (2019-nCoV) was subsequently named Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses.4 On 11th February, 2020, the World Health Organization (WHO) gave an official name to the disease caused by the virus as Corona Virus Disease 2019 (COVID-19)4,5.
Origin of the Virus
Early transmission dynamics indicates that the disease may have been transmitted from animals to humans in the Huanan seafood wholesale market in Wuhan, where live animals such as snakes, marmots, birds, frogs, hedgehogs, etc. are sold. Later, people who did not have any contact with the seafood market were also diagnosed with the disease, showing that there is human to human transmission. Studies show that pangolins or bats are the likely animal sources of the virus, but corona viruses are generally known to have several intermediate animal hosts; so there could be other hosts.5
Nature of the Virus
SARS-CoV-2 belongs to the beta corona virus genus. It has a single stranded, positive sense genome encapsulated by a viral membrane which is made of a lipid bilayer. Embedded in the viral membrane are the spike glycoprotein (S).This glycoprotein has high binding affinity to angiotensin-converting enzyme 2 (ACE2) on host cells. The virus binds to these receptors and make entry receptor cells where it replicates its genome materials and synthesize the required proteins using the host cell’s cellular machinery, and then buds out new virions from cell surface.4The genomic sequence of the virus shows stark resemblance to SARS and MERS corona viruses which are known to cause diseases in humans. Apart from their biochemical nature, they all belong to beta corona virus genus and bind to the same receptor (ACE 2) on human cells. Their S protein is also similar. They have similar viral proteases (3CLpro and PLpro) which they use for replication when they get into host cells.13
Available evidence shows that transmission of SARS-CoV-2 between people is through respiratory droplets and contact routes. The viral particles are encapsulated in droplets of mucus, saliva and water, which are generally 5 – 10 µm in diameter.10 Infected people release these droplets when they speak, sneeze or cough. Since they are relatively large (5-10 µm), they do not travel far from the source before falling under gravity. The droplets can fall on persons nearby (within one-meter radius) or fall on surfaces. One can become infected if such drops get into their eyes, nose or mouth. Viruses from droplets that fall on surfaces can be picked up by people when they touch those surfaces with their hands and then touch their face. COVID-19 is thus transmitted by direct contact with infected persons and indirect contact with surfaces in the immediate environment of infected persons.11 At present, there is no conclusive evidence that the virus is transmitted through air in aerosols.10
This virus is highly infectious. It infected over seventy thousand people in China within the first fifty days of its emergence.12The first case of COVID-19 outside China was reported in Thailand on 13th January, 2020.6Within seven months, infections spread all over the world, affecting 210 countries in six continents. As at 18th August, 2020 there were 21,896,155 confirmed cases of COVID-19 and 774,539 deaths, representing 3.54 % of infections worldwide.7 The WHO says the disease is mild in most patients and rarely fatal,over 80 % of people who contract COVID-19 present only mild symptoms and naturally recover without any medical intervention.8 The disease is, however, likely to be fatal in people who have existing chronic disease conditions such as Type 2 diabetes, cancer, sickle cell disease, asthma, heart disease, high blood pressure, etc. Elderly people are also at higher risk of fatality than children and youths.9Its symptoms include fever, cough, tiredness, loss of taste or smell, shortness of breath or difficulty in breathing, muscle aches, chills, sore throat, runny nose, headache and chest pain. These symptoms are not all inclusive; some patients may have only a few of them while others may remain asymptomatic. Symptoms usually appear two to fourteen days after exposure to the virus9. It is advisable to consult medical personnel as soon as one begins to experience any of these symptoms.
At present no drug has been approved for the treatment of COVID-19. In the absence of approved chemotherapy, prevention is the most viable option for controlling the pandemic. Prevention is primarily aimed at stopping the transmission of the virus. Knowledge of the virus’ physical and biochemical nature has been useful in designing the prevention protocol.26Regular washing of hands with soap and water is advised because soap is a surfactant and thus destroys the lipid bi-layer by emulsification which causes the glycoprotein spikes to fall off from the viral membrane, thus making the virus unable to bind to host receptor cells. Emulsification of the lipid bilayer also allows little amount of soapy water to enter inside the virus which destroys it. Use of alcohol-based hand sanitizers also helps to protect against the virus. Hand sanitizers contain at least 60% ethanol or isopropyl alcohol, which are typical organic solvents capable of dissolving the lipid bilayer in the viral membrane. People are also advised to avoid touching their hands on the face when they touch surfaces in public places in order to minimize the risk of getting infected with viral particles from droplets that may have fallen on such surfaces from infected persons.11
Since China was the first to experience this novel disease, the rest of the world has had to learn a lot from their approach to its management. The clinical manifestation of the disease is classified into four levels of severity: mild, moderate, severe and critical.14Management entails providing symptomatic treatment and supportive care which may include bed rest, adequate diet, water and electrolyte balance and monitoring of vital signs15. WHO recommends the use of antipyretics for the symptomatic management of the fever, which is the most common symptom of the disease.15 In severe or critical conditions, artificial respiration by mechanical ventilators has been used.16At present, there are no approved drugs for the treatment of COVID-19. Knowledge of the biochemical nature and mechanism of viral infection on host cells is also still evolving. Physicians have relied on information from similar infections in the past to provide care and management of the disease. Anti-viral drugs for infections presumed to have similar mechanism of viral infections are being considered for treatment of COVID-19; and in some cases have been discretionally used for the treatment of the disease. The RNA polymerase inhibitor, Remdesivir (a nucleotide adenosine analogue antiviral drug for Ebola virus) has been used for treatment of COVID-19 in the USA, China and other countries.17 Other nucleoside analogues (tenofovirdisoproxil, lamivudine, Zidovidine, Stavudine, Zalcitabine, Emtricitabine, Lamividine, Alovudine, Apricitabine) are being evaluated through molecular docking studies for their potential to inhibit SARS-CoV-2 replication. The protease inhibitor drugs, Lopinavir and Ritonavir have also been used.4 Hydroxychloroquine (a heterocyclic antimalarial drug) has also been used alone or in combination with azithromycin (an antibiotic mostly used for treatment of pneumonia and other respiratory tract infections) to treat COVID-19. In the early days of the pandemic, many countries authorized the hospital use of hydroxychloroquine for treatment under the supervision of healthcare professionals.18 WHO and the United State of America’s Food and Drug Administration (FDA) later issued a caution against its use and suspended the solidarity trials of hydroxychloroquine which were ongoing, citing concerns that it could be toxic and induce heart disease. Many people have criticized this decision, as being more political than scientific. WHO has been accused of deliberately ignoring scientific studies whose findings clearly show that hydroxychloroquine and azithromycin actually cure COVID-19.23-25 President Trump of the United States said he took hydroxychloroquine as prophylaxis against the disease. Brazilian President, Jair Bolsonaro after being treated with azithromycin is quoted to have said “we know that there is no scientific evidence, but it has worked with me”.19 Other scientific studies and testimonies by individuals who used hydoxychloroquine for treatment of COVID-19 show that it is a less toxic derivative of chloroquine and is effective in inhibiting SARS-CoV-2 infection with minimal side effects.20,21,22
In the absence of approved drugs for its treatment, a vaccine would be the most potent way to contain the virus. Russia has outrun other nations in the race to produce COVID-19 vaccine. However, President Vladimir Putin’s announcement on Tuesday, 11th August, 2020 that Russia’s Gamaleya Research Institute has produced the first COVID-19 vaccine has met criticism. Western scientists are concerned that the safety of the vaccine has not been adequately determined. Russia however has dismissed the criticism. The Russian vaccine, Sputnik-V is named after the Soviet era satellite that was the first to be launched into space in 1957. Russia projects that mass production of the vaccine will start by September, 2020 with production reaching five million doses per month by January, 2021.27
Hydroxychloroquine, Azithromycin Lopinavir and Ritonavir Remdesivir
Some compounds that have been used for treatment of COVID-19
- Juengling, F.D., Maldonado, A., Wuest, F. and Schindler, T.H. (2020). Who was the first doctor to report the COVID-19 outbreak in Wuhan China? The Journal of nuclear medicine, 61(6): 782 – 783
- Badawi, A. andRyoo, S.G. (2016). Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. International Journal of Infectious Diseases, 49: 129–133.
- Vijayanand, M.W. Wilkins. Severe acute respiratory syndrome (SARS): a review. Clin. Med. (Northfield. Il). 2004, 4 (2), 152.
- Chikara, B.S., Rathi, B., Singh, J. and Poonam (2020). Corona virus SARS-CoV-2 disease COVID-19: Infection, prevention and clinical advances of the prospective chemical drug therapeutics. Chemical Biology Letters7(1): 63-72
- El-Aziz, T.M. and Stockand, J.D. (2020). Recent progress and challenges in drug development against coronavirus (SARS-CoV-2) – an update on the status. Infection, Genetics and Evolution, 83(2020): 1-10
- WHO (2020). Archive: WHO timeline – COVID-19. Accessed on 18th August. 2020 from https://www.who.int/news-room/detail/27-04-2020-who-timeline—covid-19
- European Centre for Disease Prevention and Control -ECDC, (2020). COVID-19 situation update worldwide, as of 18 August 2020. Accessed ono 18th August, 2020 from https://www.ecdc.europa.eu/en/geographical-distribution-2019-ncov-cases
- Unhale, S.S., Ansar, Q.B., Sanap, S., Thakhre, S., Wadatkar, S., Bairagi, R., Sagrule, S. and Biyani, K.R. (2020). A review on corona virus (COVID-19). World Journal of Pharmaceutical and Life Sciences, 6(4): 109 – 115
- MAYO CLINIC (2020). Coronavirus disease 2019 (COVID-19). Accessed ono 18th August 2020 from https://www.mayoclinic.org/diseases-conditions/coronavirus/symptoms-causes/syc-20479963
- Mahesh Jayaweera,a,∗HasiniPerera,b BuddhikaGunawardana,a and JagathManatunge (2020). Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environmental Research; 188: 109819. doi: 1016/j.envres.2020.109819
- WHO (2020). Modes of transmission of virus causing COVID-19: implications for IPC precaution recommendations. Accessed 18th August 2020 fromhttps://reliefweb.int/sites/reliefweb.int/files/resources/WHO-2019-nCoV-Sci_Brief-Transmission_modes-2020.1-eng.pdf
- Muhammad Adnan Shereen a,b,1 , Suliman Khan a,1,⇑, AbeerKazmi c , Nadia Bashir a , Rabeea Siddique a (2020). COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses. Journal of Advanced Research24: 91–98.
- Zhou, A. and Liu, C. (2020). Chemists Fighting COVID-19 – A Global Conversation. Accessed on 19th August, 2020 from https://youtube/xzpX7qeB8Vg
- Peng, P., Tu, L., Yang, Y., Hu, P., Wang, R., Hu, O., Cao, et al. (2020). Management and Treatment of COVID-19: The Chinese Experience. Canadian Journal of Cardiology, 36: 915 – 930
- World Health Organisation. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. 2020. Available at:https://www.who.int/publications-detail/clinical-managementof-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infectionis-suspected. Accessed August 13, 2020.
- Guan W.J., Ni, Z,Y. and Hu, Y. (2020). Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382: 1708-20.
- Fan, L., Jiang, S., Yang, X., Wang, Z. and Yang, C. (2020). COVID-19 treatment in China. Current Pharmacology Reports, 6: 146 – 154.
- Goodman, J. and Giles, C. (2020). Coronavirus and hydroxychloroquine: What do we know? https://www.bbc.com/news/51980731
- Trump had no side effects after taking hydroxychloroquine, white house doctor says. https://www.cnbc.com/2020/06/03trump-had-no-side-effects-after-taking-hydroxychloroquine-white-house-doctor-says.html
- Liu, J., Cao, R., Xu, M., Wang, X., Zhang, H., Hu, H. and Li, Y. (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discovery6(16): 1-4
- Li, X., Wang, Y., Agostinis, A., Rabson, A., Melino, G., Carafoli, E., et al. (2020). Is hydroxychloroquine beneﬁcial for COVID-19 patients? Cell Death and Disease11(512): 1-6
- Monteiro, E.M.R., Nascimento, M.F.L., Brito, T.R.C., Lima, M.C., Sefair, L.R. and Pedrosa, M.M (2020) Chloroquine and COVID-19: Should We Care about Ototoxicity? International Archives of Otorhinolaryngology4(3): 359 – 363
- Martinez, J.C. (2020). Chemists Fighting COVID-19 – A Global Conversation. Accessed on 19th August, 2020 from https://youtube/xzpX7qeB8Vg
- Ichoron and Igoli are academic staff of Department of Chemistry, University of Agriculture Makurdi, Benue State.