biostudies-literatureFerrer-Orta CPLATESA2 from Comunidad de Madrid/FEDERMinisterio de Ciencia e Innovación (MCIN)MEC | Instituto de Salud Carlos IIIMEC | Consejo Superior de Investigaciones Científicas (CSIC)Fundació La Marato TV3MEC | Instituto de Salud Carlos III (ISCIII)Fundació La Marato TV3Ministerio de Ciencia e InnovaciónMEC | Consejo Superior de Investigaciones Científicase2317977121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11260105biostudies-literatureUnknown121(29)In a recent characterization of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variability present in 30 diagnostic samples from patients of the first COVID-19 pandemic wave, 41 amino acid substitutions were documented in the RNA-dependent RNA polymerase (RdRp) nsp12. Eight substitutions were selected in this work to determine whether they had an impact on the RdRp activity of the SARS-CoV-2 nsp12-nsp8-nsp7 replication complex. Three of these substitutions were found around the polymerase central cavity, in the template entry channel (D499G and M668V), and within the motif B (V560A), and they showed polymerization rates similar to the wild type RdRp. The remaining five mutations (P323L, L372F, L372P, V373A, and L527H) were placed near the nsp12-nsp8_F contact suProceedings of the National Academy of Sciences of the United States of AmericaPoint mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.PMC11260105PI21/00139FI19/00119CSIC-COV19-014PID2020-117976 GB-I00202136-31202136-30PID2020-113888RB-I00S2018/BAA-4370202220I116Verdaguer NDomingo EVazquez-Monteagudo SFerrer-Orta CMartinez-Gonzalez BPerales CFerrero DSfalsePoint mutations at specific sites of the nsp12-nsp8 interface dramatically affect the RNA polymerization activity of SARS-CoV-2.In a recent characterization of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variability present in 30 diagnostic samples from patients of the first COVID-19 pandemic wave, 41 amino acid substitutions were documented in the RNA-dependent RNA polymerase (RdRp) nsp12. Eight substitutions were selected in this work to determine whether they had an impact on the RdRp activity of the SARS-CoV-2 nsp12-nsp8-nsp7 replication complex. Three of these substitutions were found around the polymerase central cavity, in the template entry channel (D499G and M668V), and within the motif B (V560A), and they showed polymerization rates similar to the wild type RdRp. The remaining five mutations (P323L, L372F, L372P, V373A, and L527H) were placed near the nsp12-nsp8_F contact su2024-01-01T00:00:00Z2024 Jul2026-06-01T19:36:44.433Z2025-02-19T02:01:53.861ZS-EPMC112601053899094110.1073/pnas.2317977121