Mapping Potential Drug Resistance Mutations in SARS-CoV-2 nsp12 Motifs Q1 2025

This study investigates mutations in conserved motifs of the SARS-CoV-2 nsp12 (RNA-dependent RNA polymerase) from genomic sequences collected between January and April 2025 (Q1) Mutations were analyzed in four key functional motifs: A, C, F, and G , which are involved in viral replication and known targets for antiviral drugs such as Remdesivir , Molnupiravir , and Favipiravir . Sequences were aligned using MAFFT , translated into amino acid sequences, and scanned for mutations at known resistance-associated positions. Findings: Motif A (Positions: D614, P621, N623)D614X : Found in multiple isolatesP621X : Detected in several sequencesN623X : Observed frequentlyThese mutations are located near the active site of RdRp and may affect polymerase efficiency and drug binding. Motif C (Positions: L655, V657)L655X : Found in several sequencesV657X : Commonly observedThese positions are implicated in Remdesivir resistance in prior studies. Motifs F and GNo reliable mutations could be identified due to: Alignment gapsTruncated sequencesPoor coverage in motif regionsFurther analysis with complete sequences is recommended. Potential Implications for Antiviral DrugsMutations in motifs A and C may reduce efficacy of:RemdesivirMolnupiravirOther nucleoside analogs targeting RdRpNote: I did this study independently, it is non-clinical research based on publicly available sequence data. No conclusions should be used for diagnosis, treatment, or policy without further validation.