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Diversity due to mutations in circulating virus strains of SARS-CoV-2 may delay control of COVID-19

Sharanagouda S. Patil, Chandan Shivamallu, Chandan Dharmashekara, Sushma Pradeep, Kuralayanapalya Puttahonnappa Suresh, Ashwini Prasad, Shiva Prasad Kollur, Mahendra P. Yadav, Chandrashekar Srinivasa, Bramhadev Pattnaik.

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Severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) is a beta-coronavirus (beta- CoV; sarbecovirus), like its predecessors SARS and MERS CoVs. Of the structural proteins of the virus, the Spike (S) protein on the virion envelope binds to the host cell ACE2 through viral epitopes in the receptor-binding domain (RBD). Deletions in the ORF8 as well as mutations in the S gene of SARS-CoV of 2003 were related to adaptation of the virus to humans. The emergence of novel variants of SARS-CoV-2, viz., B.1.1.7, B.1.427 and B.1.429, B.1.617 and its Kappa and Delta strains/ variants, B.1.351, and P.1 in the United Kingdom, Americas, India, South Africa and Brazil, respectively, has been found be associated with the current waves of the COVID-19 pandemic. These variants are antigenically dissimilar, whereas the current COVID-19 vaccines are monovalent. This is a handicap in the control program. The Delta variant has been reported in 74 countries as of 14 June 2021 and the anticipated third wave involving this variant is of concern to the countries (www.gavi.org). Of late, on 17 June 2021, Delta Plus variant was identified in India (AIIMS, Bhopal, India). Circulation of virus in vaccinated population may lead to endemicity, and this can be monitored by regular serosurveillance for antibodies against select non-structural proteins (NSPs) of the virus; antibodies to NSPs will indicate virus replication in the host. Endemic areas will have higher NSP reactors. It is predicted that the Delta B.1 variant may ignite the third wave of the disease in many countries. As it has been difficult to achieve uniformity in time and density of the vaccination even in the districts, circulation of the virus in partially immune population may lead to the selection of newer variants of SARS-CoV-2. The presence of monoclonal antibody resistant mutants and neutralization—escape mutants in quasispecies structure of another + sense RNA virus, i.e., Aphthovirus (FMD virus; foot and mouth disease virus) in the family Picornaviridae is well documented. The situation could be similar in the Coronaviridae member SARS-CoV-2. Previous immunity may not protect against current/ future mutants thereby pro-longing the COVID-19 control Programme.

Key words: SARS-CoV-2, COVID-19, RNA viruses, Quasispecies, neutralization escape mutants, Non-structural proteins, Serosurveillance, DIVA/ DIVI.

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