Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutant receptor-binding domain with ACE2

Dash, Pujarini; Turuk, Jyotirmayee; Behera, Santosh Ku; Palo, Subrata Kumar; Raghav, Sunil K.; Ghosh, Arup; Sabat, Jyotsnamayee; Rath, Sonalika; Subhadra, Subhra; Rana, Khokan; Bhattacharya, Debdutta; Kanungo, Srikanta; Kshatri, Jaya Singh; Mishra, Bijaya Kumar; Dash, Saroj; Parida, Ajay

doi:10.1016/j.ijid.2021.01.020

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…Viruses identified in the two countries played key roles in forming the core of clusters in the transmission network. The mutant strains in both countries showed possible higher infectivity and antigenicity than SARS-CoV-2 strains at the early stage [ 40 , 41 ]. Mutant strains including B.1.617 were epidemic in India, according to the reports of the WHO.…”

Section: Discussionmentioning

confidence: 99%

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

et al. 2021

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Background The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is pandemic. However, the origins and global transmission pattern of SARS-CoV-2 remain largely unknown. We aimed to characterize the origination and transmission of SARS-CoV-2 based on evolutionary dynamics. Methods Using the full-length sequences of SARS-CoV-2 with intact geographic, demographic, and temporal information worldwide from the GISAID database during 26 December 2019 and 30 November 2020, we constructed the transmission tree to depict the evolutionary process by the R package “outbreaker”. The affinity of the mutated receptor-binding region of the spike protein to angiotensin-converting enzyme 2 (ACE2) was predicted using mCSM-PPI2 software. Viral infectivity and antigenicity were tested in ACE2-transfected HEK293T cells by pseudovirus transfection and neutralizing antibody test. Results From 26 December 2019 to 8 March 2020, early stage of the COVID-19 pandemic, SARS-CoV-2 strains identified worldwide were mainly composed of three clusters: the Europe-based cluster including two USA-based sub-clusters; the Asia-based cluster including isolates in China, Japan, the USA, Singapore, Australia, Malaysia, and Italy; and the USA-based cluster. The SARS-CoV-2 strains identified in the USA formed four independent clades while those identified in China formed one clade. After 8 March 2020, the clusters of SARS-CoV-2 strains tended to be independent and became “pure” in each of the major countries. Twenty-two of 60 mutations in the receptor-binding domain of the spike protein were predicted to increase the binding affinity of SARS-CoV-2 to ACE2. Of all predicted mutants, the number of E484K was the largest one with 86 585 sequences, followed by S477N with 55 442 sequences worldwide. In more than ten countries, the frequencies of the isolates with E484K and S477N increased significantly. V367F and N354D mutations increased the infectivity of SARS-CoV-2 pseudoviruses (P < 0.001). SARS-CoV-2 with V367F was more sensitive to the S1-targeting neutralizing antibody than the wild-type counterpart (P < 0.001). Conclusions SARS-CoV-2 strains might have originated in several countries simultaneously under certain evolutionary pressure. Travel restrictions might cause location-specific SARS-CoV-2 clustering. The SARS-CoV-2 evolution appears to facilitate its transmission via altering the affinity to ACE2 or immune evasion. Graphic Abstract

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Section: Discussionmentioning

confidence: 99%

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

et al. 2021

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“…It remains to be investigated in controlled clinical studies whether lecithin-based therapies may contribute to improve therapeutic measures, reduce infections and improve containment of the enduring COVID-19 pandemic. Another area that deserves attention are the role of mutants [ 106 , 107 ] in how they may change the binding affinity of putative blockers of SARS-CoV-2 RBD. The mechanisms of the efficiency of POPC action on mutants is beyond the scope of this paper, yet we can only speculate that mutants that enhance the exposure of hydrophobic groups in the RBD domain may enhance the binding of POPC.…”

Section: Discussionmentioning

confidence: 99%

Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy

et al. 2021

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“…The mutations potentially provide the virus with abilities to enhance infectivity through altered adhesion machinery, escape immune protection and vaccination, and spread beyond species, as evidence by Indian strains. 1 , 2 , 3 Artificial mutation of the virus can even cause infection to mice. 4 Given that we can hardly predict the end of the infected world, it can safely be said that we definitely need to struggle against life‐threatening severe manifestations of COVID‐19.…”

Section: Prefacementioning

confidence: 99%

“…17 Cell components in bronchoalveolar lavage fluid (BALF) revealed a prominent increase in neutrophils in COVID-19 as compared with other pneumonias. 18 This raises at least four fundamental questions of, [1] which cells specifically produce S100A8 upon infection, [2] whether or not S100A8 upregulation is specific to SARS-CoV-2, [3] why canonical antibacterial neutrophils transmigrate through epithelial barrier to alveolar space in this particular viral infection, and [4] what connects infection with activation of coagulation cascade.…”

Section: Evidence From Patientsmentioning

confidence: 99%

“…The pandemic allows severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to acquire mutations after tremendous chances of replication in human body. The mutations potentially provide the virus with abilities to enhance infectivity through altered adhesion machinery, escape immune protection and vaccination, and spread beyond species, as evidence by Indian strains 1–3 . Artificial mutation of the virus can even cause infection to mice 4 .…”

Section: Prefacementioning

confidence: 99%

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S100A8 may govern hyper‐inflammation in severe COVID‐19

et al. 2021

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The coronavirus disease 2019 (COVID‐19) pandemic threatens human species with mortality rate of roughly 2%. We can hardly predict the time of herd immunity against and end of COVID‐19 with or without success of vaccine. One way to overcome the situation is to define what delineates disease severity and serves as a molecular target. The most successful analogy is found in BCR‐ABL in chronic myeloid leukemia, which is the golden biomarker, and simultaneously, the most effective molecular target. We hypothesize that S100 calcium‐binding protein A8 (S100A8) is one such molecule. The underlying evidence includes accumulating clinical information that S100A8 is upregulated in severe forms of COVID‐19, pathological similarities of the affected lungs between COVID‐19 and S100A8‐induced acute respiratory distress syndrome (ARDS) model, homeostatic inflammation theory in which S100A8 is an endogenous ligand for endotoxin sensor Toll‐like receptor 4/Myeloid differentiation protein‐2 (TLR4/MD‐2) and mediates hyper‐inflammation even after elimination of endotoxin‐producing extrinsic pathogens, analogous findings between COVID‐19‐associated ARDS and pre‐metastatic lungs such as S100A8 upregulation, pulmonary recruitment of myeloid cells, increased vascular permeability, and activation coagulation cascade. A successful treatment in an animal COVID‐19 model is given with a reagent capable of abrogating interaction between S100A8/S100A9 and TLR4. In this paper, we try to verify our hypothesis that S100A8 governs COVID‐19‐associated ARDS.

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Sequence analysis of Indian SARS-CoV-2 isolates shows a stronger interaction of mutant receptor-binding domain with ACE2

Cited by 5 publications

References 30 publications

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Characterization of SARS-CoV-2 worldwide transmission based on evolutionary dynamics and specific viral mutations in the spike protein

Phospholipids dock SARS-CoV-2 spike protein via hydrophobic interactions: a minimal in-silico study of lecithin nasal spray therapy

S100A8 may govern hyper‐inflammation in severe COVID‐19

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