key: cord-1031727-v084s16j
authors: Chakraborty, Chiranjib; Bhattacharya, Manojit; Sharma, Ashish Ranjan
title: Emerging mutations in the SARS-CoV-2 variants and their role in antibody escape to small molecule-based therapeutic resistance
date: 2021-11-22
journal: Curr Opin Pharmacol
DOI: 10.1016/j.coph.2021.11.006
sha: 9b3538674c89a7335e330820d3946907d3efccfa
doc_id: 1031727
cord_uid: v084s16j

Several clinical trials started during the COVID-19 pandemic to discover effective therapeutics led to identifying a few candidates from the major clinical trials. However, in the past several months, quite a few SARS-CoV-2 variants have emerged with significant mutations. Major mutations in the S-glycoprotein and other parts of the genome have led to the antibody's escape to small molecule-based therapeutic resistance. The mutations in S-glycoprotein trigger the antibody escape/resistance, and mutations in RdRp might cause remdesivir resistance. The article illustrates emerging mutations that have resulted in antibody escape to therapeutics resistance. In this direction, the article illustrates presently developed neutralizing antibodies (with their preclinical, clinical stages) and antibody escapes and associated mutations. Finally, due to the RdRp mutations, the antiviral small molecules resistance is illustrated.

these mutations, antibody escape activity is more common [22] . 157 The same research group has performed an experiment using the replication-competent of a 158 chimeric virus. The study used rVSV encoding a green fluorescent protein and S-159 glycoprotein of SARS-CoV-2 (rVSV/SARS-CoV-2/GFP) [23] . This experiment has adapted 160 two high-titer variants of this recombinant construct (rVSV/SARS-CoV-2/GFP) and 161 generated three to four passages. The genome was sequenced during the passage experiment 162 (third or fourth passage), and the mutations were analyzed.. Here, researchers found those 163 mutations with high frequency in S-glycoprotein (E484K, N440K, F490L, Q493K) [24] . 164 Another study reported C144 resistance mutations (Q493R/K and E484K/A/G) using SARS- 165 CoV-2/ rVSV. The study revealed that E484K mutation substitution causes resistance to two The first mutation was observed D614G in the S-glycoprotein. The mutation is located S1 520 subunit near the S1/S2 boundary, and the furin cleavage site is also found in this particular 521 point (S1/S2 boundary). All the figures were generated using any of the two PDB ID 522 (6ZP0 and 7DK3). 

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