Neutralizing antibodies and their cocktails against SARS-CoV-2 Omicron and other circulating variants

Severe acute respiratory coronavirus 2(SARS-CoV-2),the causative agent of coronavirus disease 2019(COVID-19),has led to a pandemic with severe economic losses.The viral surface spike(S)protein comprises two subunits:S1 and S2.S1 contains an N-terminal domain(NTD)and a C-terminal domain(CTD)(i.e.,the receptor binding domain(RBD))[1,2].The RBD itself comprises core and receptor binding motif(RBM)regions(Fig.1a).During virus infection in humans,the RBD of S1 binds to the cellular receptor angiotensin-converting enzyme 2(ACE2)(Fig.1b),and S2 mediates viral entry and membrane fusion[1,3].Thus,the S protein is a critical vaccine and therapeutic target.The prefusion S protein exists as a trimer consisting of three RBDs;of these,the RBD in the“up”confirmation binds to ACE2(Fig.1c).SARS-CoV-2 has undergone frequent mutations since its emergence in 2019,and a number of mutated S protein residues have been identified,including in the RBD.Alpha(B.1.1.7),Beta(B.1.351),and Gamma(P.1)are previously circulating variants of concern(VOCs);in contrast,Delta(B.1.617.2),Omicron(B.1.1.529)BA.1,and other Omicron subvariants(BA.2,BA.3,BA.4,and BA.5),as well as BA.1/BA.2 circulating recombinant forms such as XE,are currently circulating VOC strains[4].Compared with the original SARS-CoV-2,the Omicron variant carries more mutations than any other variant identified thus far,among which approximately 39 and 15 substitutions are within the S protein and RBD,respectively,of the BA.1 subvariant.