Dataset Information

SARS-CoV-2-RELATED BAT VIRUS BEHAVIOR IN HUMAN-RELEVANT MODELS SHEDS LIGHT ON THE ORIGIN OF COVID-19

ABSTRACT: Bat sarbecovirus BANAL-236 is highly related to SARS-CoV-2 and infects human cells, albeit lacking the furin cleavage site in its spike protein. BANAL-236 replicates efficiently and pauci-symptomatically in humanized mice and in macaques, where its tropism is enteric, strongly differing from that of SARS-CoV-2. BANAL-236 infection leads to protection against superinfection by a virulent strain. We find no evidence of antibodies recognizing bat sarbecoviruses in populations in close contact with bats in which the virus was identified, indicating that such spillover infections, if they occur, are rare. Six passages in humanized mice or in human intestinal cells, mimicking putative early spillover events, select adaptive mutations without appearance of a furin cleavage site and no change in virulence. Therefore, acquisition of a furin site in the spike protein is likely a pre-spillover event that did not occur upon replication of a SARS-CoV-2-like bat virus in humans or other animals. Other hypotheses regarding the origin of the SARS-CoV-2 should therefore be evaluated, including the presence of sarbecoviruses carrying a spike with a furin cleavage site in bats.

SUBMITTER: Dr. Sarah Temmam

PROVIDER: S-SCDT-10_15252-EMBR_202256055 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:The recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 1.21 million cases of SARS-CoV-2 infection and more than 67,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. The World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted COVID-19 as a pandemic now. Multiple sequence alignment data correlated with the already published reports on SARS-CoV-2 evolution indicated that this virus is closely related to the bat severe acute respiratory syndrome-like coronavirus (bat SARS-like CoV) and the well-studied human SARS coronavirus (SARS-CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins contains molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of SARS-CoV-2 proteome will have important implications in understanding the structural and non-structural biology of SARS or SARS-like coronaviruses.

Dataset Information

SARS-CoV-2-RELATED BAT VIRUS BEHAVIOR IN HUMAN-RELEVANT MODELS SHEDS LIGHT ON THE ORIGIN OF COVID-19

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets