key: cord-0929697-9zm0qqj5 authors: Paniri, Alireza; Hosseini, Mohammad Mahdi; Akhavan-Niaki, Haleh title: Impact of new UK (B.1.1.7) SARS-Cov-2 variant on interacting with ACE2 and host immune response date: 2021-09-03 journal: Gene Rep DOI: 10.1016/j.genrep.2021.101342 sha: e9978b95f180f881e8533243f5d02097f4daa2b3 doc_id: 929697 cord_uid: 9zm0qqj5 nan docking results achieved with both tools have suggested that VUI-202012/ 01 can bind to ACE2 with higher affinity in comparison with the two other variants, and may increase cell entry capacity and transmissibility of the new variant of SARS-CoV-2 (Table 1) . Accordingly, Ramanathan et al. have shown that the B.1.1.7 variant harboring the N501Y mutation show a twofold stronger binding affinity to ACE2in comparison with SARS-CoV-2. Interestingly, it has also been demonstrated that the B.1.351 variant first detected in South Africa and carrying three mutations (E484K, N501Y, and K417N) binds to ACE2 with a five times stronger affinity than SARS-CoV-2 (Ramanathan et al., 2021) . Furthermore, in silico investigation by Villoutreix et al. has revealed that N501Y (identified in both the UK and South African strains) influence Spike-ACE2 interaction, and consequently increases transmissibility and possibly its pathogenicity while the K417N and E484K substitutions (South African strain) showed no significant impact (Villoutreix et al., 2021) . Consistently, in silico analysis of ACE2-S protein interaction conducted by Singh et al. and Ortega et al. have revealed that N501Y might raise the affinity of S protein with host receptor (Ortega et al., 2021; Singh et al., 2021) . It is interesting to mention that Calcagnile et al. have reported that ACE2 missense variant K26R shows increased affinity for SARS-CoV-2 Spike protein which is more common in European and American populations (Calcagnile et al., 2021) . Furthermore, bioinformatics and structural approaches analysis conducted by Spratt et al. have shown that D614G in Spike protein and P323L in RNA polymerase which are present in new variants may increase SARS-CoV-2's infectivity in comparison with SARS-CoV variant (Spratt et al., 2021) . Nonetheless, results from interaction studies between TMPRSS2 and S protein showed no significant difference among the three SARS-CoV-2 variants (Table 2 and Fig. 1) . Strikingly, analyses of protein epitopes using the Immune Epitope Database (IEBD) (https://www.iedb.org/) has revealed a significant difference between epitope profiles of the original Wuhan strain, the SARS-CoV-2 D614G mutant, and the B.1.1.7 variant (Table 2) . It has been shown that B.1.1.7 has 409 unique epitopes with high prediction score that are identified by specific antigen-presenting cells containing MHC-II while these epitopes have not been found in SARS-CoV-2 and D614G strain. On the other hand, 6 specific epitopes were detected for B.1.1.7 that might be identified by cells containing MHC-I in comparison with SARS-CoV-2 and D614G strain. Surprisingly, IEBD has also shown that 4 of 17 B.1.1.7 mutations including N501Y, A570D, T716I, and D1118H are located in epitopes that may be identified by antibodies, and consequently hosts might show a different response to this new variant in comparison with the two other COVID-19 variants. Interestingly, further analysis by PHYRE2 (http://www.sbg.bio.ic.ac. uk/~phyre2/html/page.cgi?id=index) has indicated that N501 has a low conservation score, and is sensitive to mutations as we see in the B.1.1.7 S protein (N501Y). Furthermore, ligand binding site investigated by ITASSER (https://zhanglab.ccmb.med.umich.edu/I-TASSER/) has revealed a significant change in ligand binding site of the B.1.1.7 S protein (874, 877, 878) in comparison with D614G variant (294, 297, 298, 301) highlighting the possible impact of new mutations on interaction of the B.1.1.7 S protein with different cell receptors, SARS-CoV-2 virulence, and host immune responses. Collectively, our molecular docking results suggest that B.1.1.7 might bind more tightly to ACE2, and may therefore become more virulent. Although, there is a IPTNFTISVTTEIL PTNFTISVTTEIL AIPTNFTISVTTEI AIPTNFTISVTTEIL TNFTISVTTEILPV IPTNFTISVTTEI IAIPTNFTISVTTEI TNFTISVTTEIL PTNFTISVTTEILP TNFTISVTTEILP IPTNFTISVTTEIL PTNFTISVTTEIL AIPTNFTISVTTEI AIPTNFTISVTTEIL TNFTISVTTEILPV IPTNFTISVTTEI IAIPTNFTISVTTEI TNFTISVTTEIL discrepancy about the rate of transmissibility of the B.1.1.7 variant, evidence thoroughly show that the B.1.1.7 variant is more virulent and there are concerns about vaccine efficacy on this variant (Leung et al., 2021; Collier et al., 2021; Wang et al., 2021; Volz et al., 2021; Muik et al., 2021) . Therefore, given the high mutation rate of SARS-COV-2, more studies need to be performed to fully elucidate the efficiency of vaccines, and thereby updating vaccines may be considered according to new variants. No funding was received for this work. Molecular docking simulation reveals ACE2 polymorphisms that may increase the affinity of ACE2 with the SARS-CoV-2 spike protein Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies Characteristics of SARS-CoV-2 and COVID-19 Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccineelicited human sera Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis First comprehensive computational analysis of functional consequences of TMPRSS2 SNPs in susceptibility to SARS-CoV-2 among different populations Comprehensive in silico identification of impacts of ACE2 SNPs on COVID-19 susceptibility in different populations SARS-CoV-2 B.1.1.7 and B.1.351 Spike variants bind human ACE2 with increased affinity Structure-function analyses of new SARS-CoV-2 variants B.1.1.7, B.1.351 and B.1.1.28.1: clinical, diagnostic, therapeutic and public health implications Factors associated with emerging and re-emerging of SARS-CoV-2 variants In silico investigation of the new UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 variants with a focus at the ACE2-spike RBD interface Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.