LA effectively inhibits SARS-CoV-2 infection regardless of S mutation
Mutations in gene encoding S protein, which were found in most of SARS-CoV-2 variants, have been reported to cause an increase in SARS-CoV-2 infectivity by enhancing attachment to ACE2 on the host cell surface (Ozono et al., 2021; Zaman, Orakzai & Yunus, 1987; Zhang et al., 2020). Among novel S mutations, D614G is the most common one found in the lineage B.1 of SARS-CoV-2 including Alpha, Beta, Delta, and Omicron variants (Schrors et al., 2021). To test whether LA can equally inhibit the enhanced SARS-CoV-2 infectivity mediated by S mutations, the D614G mutation was introduced into the S gene by site-directed mutagenesis. Consistent with previous studies, pSARS-CoV-2 carrying the D614G mutation showed a significantly higher infectivity compared to the wild type (WT) in both ACE+ and ACE2/TMPRSS2+ cells (Figure 5a). Importantly, LA treatment blocked the entry of the D614G mutant virus with IC50 of 2.02 and 2.99 μM in ACE2+ and ACE2/TMPRSS2+ cells respectively (Figure 5b), which were comparable to those of the WT virus (Figure 2a and 2b), indicating that LA effectively inhibits SARS-CoV-2 infection regardless of S mutation.