Stereoisomerism in the field of pharmaceutical sciences

Comparative study of three different coronaviruses: SARS, MERS, and COVID-19.

Netra P. Neupane, Aman K. Das

Department of Pharmaceutical Sciences, Sam Higginbottom University of Agriculture, Technology and Sciences, Prayagraj, U.P., India, 211007

Abstract:

Coronavirus is enveloped, non-segmented, single-stranded, positive-sense RNA viruses. The novel coronavirus (2019-nCoV) has been declared a pandemic by the World Health Organization on 11^th March 2020. Accessing lots of literature and research paper we reviewed origin, history, genomics and epidemiology of SARS, MERS and COVID-19. The genomics of COVID-19 partially resembled that of SARS and MERS indicating a common origin from the bat. All three viruses possess specific accessory proteins as a distinctive feature. These coronaviruses have a different incubation period, basic reproduction number (R0), accessory proteins, case fatality ratio, etc. These human coronaviruses have similarity in terms of causing respiratory illness. The transmission of coronaviruses is suspected to be zoonotic, direct human to the human transmission when in close contact, via droplet and sputum of the infected person and indirectly through touching surfaces like metal, paper, plastic, etc. The fatality of these coronaviruses is greatly inclined towards elderly people with pre-existing hepatic or digestive co-morbidities and patients with travel history from highly infected countries. Protease inhibitor like lopinavir/ritonavir along with ribavirin; ramdesivir, hydroxychloroquine have shown promising result in antiviral therapy at the initial stage of the disease. These viral pandemics in the last two decades can help human for future preparedness plans and combating diseases progression.

Keywords: SARS, MERS, COVID-19, Genomics, Zoonotic

Introduction:

Coronaviruses belong to the family coronaviridae which comprises of a large number of virus that is naturally found in birds and mammals. First human coronavirus was identified in the 1960s showing large respiratory infections in children and adults. The scientists and researchers gained attention towards human coronaviruses only after 2002 outbreak in Southern China. The virus was initially detected in Himalayan palm civets which served as the virus amplification host. Civet virus has genomics of 29 nucleotides sequence that was not found in humans. Open reading frames (ORFs) are accessory proteins which are responsible for the trans-species jump. Later, a similar virus was also found in horseshoe bats. A 29bp addition of ORF8 in bat SARS coronavirus genome is not found in most human SARS coronavirus and bats may be considered as a potential reservoir for future global pandemics.[1]

MERS is a fatal disease caused by a novel coronavirus that was first identified in 2012 in Saudi Arabia. The MERS-CoV has potentially spread from dromedary camel to humans. It may also spread from ill people to health worker and care persons through close contact. MERS-CoV is similar to SARS-CoV in genomics and associated with serious respiratory infections.[2][3][4]

COVID-19 is a novel coronavirus first identified in Wuhan city of China, from where it spread to other cities and across the world. COVID-19 is considered to have a zoonotic origin but may also transmit via the respiratory tract, direct contact and possibly through patient’s excreta having the living virus. COVID-19 outbreak at the end of December 2019 and WHO declared it as a pandemic on 11^th March 2020. Although SARS-CoV, MERS-CoV and COVID-19 belongs to the same family but COVID-19 is creating a global economic and social crisis as there is no primary medicines and vaccines for its mitigation and treatment. Also, the number of cases of COVID-19 are rising exponentially day by day.[5][6]

Table 1: Comparison of SARS, MERS, and COVID-19[7][8][9][10]

S.N	Contents	COVID-19	MERS	SARS
1.	Place of origin	Wuhan, China	Jeddah, Saudi Arabia	Guangdong, China
2.	Outbreak year	2019	2012	2002
3.	Animal reservoir	Specific species is yet not confirmed (potentially Bat).	Dromedary Camel	Bat
4.	Incubation period (days)	2-14	2-14	10
5.	Major symptoms	Fever, Dry cough, Tiredness	Fever, Cough and Shortness of breathe	Fever, Malaise, Myalgia, Headache, Diarrhoea, and severing.
6.	Total cases	8,408,203+	2,521+	8,096+
7.	Total death	451,462+	919+	774+
8.	Case fatality ratio	9%	35%	10%
9.	Basic reproduction number(R0)	2-2.5	<1	2-4

History:

Coronavirus is not a new virus it was first found in 1960 with common cold-like symptoms. A study carried out in Canada in 2001 showed 500 patients with flu-like symptoms among them 3.6% were found positive for HCoV-NL63 strain using polymerase chain reaction. Before 2002 coronavirus was considered simple and nonfatal. In 2002-2003 Coronavirus came in new form causing Severe Acute Respiratory Syndrome (SARS) in Guangdong Province, China with approximately 10% mortality rate. It spread out of mainland China to other countries like Thailand, Hong Kong, Vietnam, Singapore, Taiwan, United States of America.  SARS infected a total of 8096 individuals out of which 774 died till 2004.[11]

 In 2012 a new form of coronavirus was identified as Middle East Respiratory Syndrome (MERS) which was isolated from the sputum of a man from Saudi Arabia who died from pneumonia and renal failure. MERS spread in 27 countries infecting a total of 2521 person, out of which 919 died. (World Health Organization) MERS had a higher mortality rate (35%) but its spread was quite slower which lead to infecting only 200 people in 18 months period.[12][13] 

The new human coronavirus (COVID-19) first appeared at the end of December 2019 in Wuhan, China. COVID-19 has affected 209 countries and territories all around the globe and two international conveyances. In comparison to SARS and MERS, it has already affected a larger number of individuals and count is increasing with  8,408,203 cases and 451,462 deaths till 10 April 2020.[14]

Genetic information:

Human coronaviruses like SARS CoV, MERS CoV and SARS CoV-2 (COVID-19) belongs to genus Beta-coronavirus and family coronaviridae. Coronaviruses are enveloped single-stranded RNA genomes with positive sense, non-segmented, club-like projection on the virus particles. The genome of the coronavirus can be divided into 3 parts, first two-part comprise of replicase genes which are translated to two large polyproteins namely pp1a and pp1ab, that through proteolytic cleavage is processed to 15 or 16 non-structural proteins (nsp). Remaining part of the genome contains ORFs for structural protein which are spikes (S), envelope (E), membrane (M) and nucleocapsid (N) proteins.[15]

In addition to coronavirus genomics, SARS-CoV has eight specific ORFs coding for accessory proteins, namely ORFs 3a, 3b, 6, 7a,  7b, 8a, 8b and 9b. These proteins do not show homology with other coronaviruses except SL-CoV-WIV1 discovered in bats.

The MERS-CoV genomics is arranged in a similar pattern to other coronaviruses along with five more putative non-structural accessory proteins; ORF3, ORF4a, ORF4b, ORF5 and ORF8b. These accessory proteins are not associated with genome replication but may carry virulence.[16][17]

COVID-19 is a spherical or pleomorphic enveloped virus possessing the largest genome (26.4-31.7kb) among all known RNA viruses. The G+C contents of COVID19 varies from 32%-43% with many small ORFs proteins present between various conserved genes (ORF1ab, spikes, envelope, membrane and nucleocapsid). The distinctive feature of COVID19 is having a unique N-terminal fragment within the spike proteins.[18]

Possible Treatment and management:

Currently, there is no vaccine or specific antiviral therapies for SARS, MERA and COVID-19. Newer therapeutic drugs are coming one after another. Protease inhibitor like lopinavir/ritonavir along with ribavirin is effective against SARS. Convalescent plasm, lopinavir and interferon (IFN) are prescribed for better management of MERS-CoV infected patients. Other effective drugs against MERS-CoV are like cyclosporin A (CsA), IFN-, omacetaxine mepasuccinate, emetine dyhydrochloride hydrate.[3] Antiviral drugs like interferon alpha-2b injection, lopinavir/ritonavir, arbidol, oseltamivir and other drugs like hydroxychloroquine and azithromycin are useful for the treatment of COVID-19. Further extensive researches and drug development work should be promoted for the development of specific antiviral therapy and vaccines.[7][19][20]

Conclusion:

Coronaviruses have affected the unprecedented number of people globally. Patients having fever and cough, travel history from infected areas or close contact with infected patients are mostly found infected. Most of the patients have developed mild symptoms while some may develop severe complication like acute respiratory distress syndrome (ARDS) and multi-organ failure. Elderly people with hepatic and digestive diseases, pregnant women, immunosuppressed and smokers are highly prone to catch viral infections. Early recognition, self-quarantine, social distancing, etc. can be very effective to decrease the rapid spread. Although tremendous efforts and research are ongoing yet still more collaborative effort is needed to accelerate the development of therapeutic medication and vaccine. Mass awareness, vigilance and surveillance should be promoted to prevent this fatal viral illness and being ready for any future challenges.

Conflict of Interest:

The authors have no conflict of interest relevant to this article.

Acknowledgement:

The authors are thankful to Sam Higginbottom University of Agriculture, Technology & Sciences. The authors are also thankful to all who contribute to fight against COVID-19.

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