An ACE2-dependent Sarbecovirus in Russian bats is resistant to SARS-CoV-2 vaccines

Abstract

Spillover of sarbecoviruses from animals to humans has resulted in outbreaks of severe acute respiratory syndrome SARS-CoVs and the ongoing COVID-19 pandemic. Efforts to identify the origins of SARS-CoV-1 and -2 has resulted in the discovery of numerous animal sarbecoviruses–the majority of which are only distantly related to known human pathogens and do not infect human cells. The receptor binding domain (RBD) on sarbecoviruses engages receptor molecules on the host cell and mediates cell invasion. Here, we tested the receptor tropism and serological cross reactivity for RBDs from two sarbecoviruses found in Russian horseshoe bats. While these two viruses are in a viral lineage distinct from SARS-CoV-1 and -2, the RBD from one virus, Khosta 2, was capable of using human ACE2 to facilitate cell entry. Viral pseudotypes with a recombinant, SARS-CoV-2 spike encoding for the Khosta 2 RBD were resistant to both SARS-CoV-2 monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Our findings further demonstrate that sarbecoviruses circulating in wildlife outside of Asia also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand

“…Although the mechanistic basis and functional consequences of more frequent responses in participants from Africa needs further study, our report underlines that our knowledge of the interplay between humans and coronavirus animal reservoirs remains vastly unexplored in Africa. Recent studies revealed that angiotensin-converting enzyme 2 (ACE2) use among bat coronavirus strains was not restricted to strains in Asia but was more broadly distributed; bat coronavirus RBD sequences from Bulgaria, Russia, and Kenya also used ACE2 (26)(27)(28)(29)(30). Further testing of animal reservoirs in Africa could elucidate whether additional bat coronavirus strains that readily use ACE2 are circulating.…”

Tissue distribution of angiotensin-converting enzyme 2 (ACE2) receptor in wild animals with a focus on artiodactyls, mustelids and phocids

“…Bats are a known natural reservoir for SARS-like viruses and harbor a diverse range of other coronaviruses, including some that utilise ACE2 receptor for cell entry [ [57] , [58] , [59] , [60] ]. Although the pandemic Sarbecoviruses (SARS-CoV and SARS-CoV-2) first emerged in Asia [ 60 ], other Betacoronaviruses including Sarbecoviruses have been detected in rhininolophus and vespertilionid bats in the Western Caucasus region of Russia and in Europe [ [61] , [62] , [63] , [64] ]. The results presented here and those reported previously [ 6 ] have demonstrated the expression of ACE2 receptors within the nasal mucosa epithelial cells of Daubenton's, pipistrelle, and serotine bats (all of which are insectivorous microchiroptera).…”

De novodesign of anti-variant COVID-19 Vaccine

“…Post-COVID world is experiencing a lot. From human infecting ability of several zoonotic viruses like monkeypox virus (61), sarbecoviruses (62), lumpy skin disease viruses (63) etc to rise of deadly viruses like dengue etc (64). All these pinpoints to the need of a combinatorial strategy for pre-priming the immune system to combat COVID like pandemic and new infections of exotic and existing viruses thereafter.…”