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These mAbs were initially developed against the wild-type SARS-CoV-2; however, emergence of variant forms of SARS-CoV-2 having mutations in the spike protein in several countries including India raised serious questions on the potential use of these mAbs against SARS-CoV-2 variants. In this study, using an <jats:italic>in silico<\/jats:italic> approach, we have examined the binding abilities of eight mAbs against several SARS-CoV-2 variants of Alpha (B.1.1.7) and Delta (B.1.617.2) lineages. The structure of the Fab region of each mAb was designed <jats:italic>in silico<\/jats:italic> and subjected to molecular docking against each mutant protein. mAbs were subjected to two levels of selection based on their binding energy, stability, and conformational flexibility. Our data reveal that tixagevimab, regdanvimab, and cilgavimab can efficiently neutralize most of the SARS-CoV-2 Alpha strains while tixagevimab, bamlanivimab, and sotrovimab can form a stable complex with the Delta variants. Based on these data, we have designed, by <jats:italic>in silico<\/jats:italic>, a chimeric antibody by conjugating the CDRH3 of regdanivimab with a sotrovimab framework to combat the variants that could potentially escape from the mAb-mediated neutralization. Our finding suggests that though currently available mAbs could be used to treat COVID-19 caused by the variants of SARS-CoV-2, better results could be expected with the chimeric antibodies.<\/jats:p>","DOI":"10.3389\/fimmu.2021.782506","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T04:50:15Z","timestamp":1641790215000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":35,"title":["In Silico Analyses on the Comparative Potential of Therapeutic Human Monoclonal Antibodies Against Newly Emerged SARS-CoV-2 Variants Bearing Mutant Spike Protein"],"prefix":"10.3389","volume":"12","author":[{"given":"Nabarun 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