“…Yountet.aland others have shown that ORF3a has been co-evolved with Spike (S) protein, suggesting the possibility of direct or indirect interactions between ORF3a and S protein [10,12,13].Studies in SARS-CoV-infected Caco2 cells show that ORF3a can be efficiently released in detergentresistant membrane structures and the diacidic motif, ExD, located within the domain VI, plays importantrole in membrane co-localisation [14].ORF3a has multi-functional roles including activating NLRP3 inflammasome and NFkB pathway, upregulating fibrinogen secretion, downregulating IFN Type Iand inducing ER stress and pro-apoptotic activity [5,[15][16][17].Therefore, mutations in this protein warrant further study to understand its role in the virulence and immune evasive potential of the recent SARS-CoV-2.Several mutations have been reported in the ORF3a gene and have been classified in the form of clades and subclades.The mutation patterns of ORF3a gene have been characterized as largely nonsynonymous(Q57H, H93Y, R126T, L127I, W128L, L129F, W131C, D155Y,S171L, D173Y, G196V, and G251V). G251V and Q57H exhibit severe virulence property [18][19][20][21].Interestingly, the 57 th position in ORF3a of pangolin SARS-CoV is H. D155Y and S171L mutations were detectedin Indian patients in May 2020 [22]. To understand the functional importance of these mutants, their characterization is needed.…”