In a recent Cell article the Chinese researchers note:
Zoonotic spillover is believed to be responsible for the outbreaks of SARS, MERS, and COVID-19.
Bats harbor the highest proportion of genetically diverse coronaviruses (CoVs) and are considered potential natural reservoirs of the three highly pathogenic human CoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2.
SARS-CoV and MERS-CoV were documented transmitted to humans via game animals (e.g., civets) or domestic animals (e.g., dromedary camels), whereas the intermediate hosts for SARS-CoV-2 remain unclear.Both in vitro and in vivo studies have demonstrated that bat merbecoviruses, which are phylogenetically related to MERS-CoV, pose a high risk of spillover to humans, either through direct transmission or facilitated by intermediate hosts
The identification of bat-related merbecoviruses in pangolins (HKU4-CoV) and minks (HKU5-CoV) suggests frequent cross-species transmission of these viruses between bats and other animal species Receptor recognition and proteolytic activation of the membrane fusion machinery are two critical steps during CoV cell entry, determining the host range and tissue tropism of the viruses.
CoV receptor engagement is mediated by receptor-binding domain (RBD) in S1 subunit of their spike (S) glycoprotein, while the membrane fusion between viral and host membranes is promoted by the S2 subunit that activated by the host proteolytic cleavage of S protein. CoVs display promiscuous receptor usage and diverse RBD-binding modes.
Dipeptidyl peptidase-4 (DPP4), angiotensin-converting enzyme 2 (ACE2), aminopeptidase N (APN), carcinoembryonic-antigen-related cell adhesion molecule 1 (CEACAM1), and transmembrane serine protease 2 (TMPRSS2) are five well-known functional protein receptors for CoVs.The same receptor usage can be shared by CoVs from different subgenera, as exemplified by the ACE2 receptor usage by human CoV NL63 (subgenus Setracovirus) and various SARSr-CoV (subgenus Sarbecovirus) with distinct RBD architechtures.
Additionally, CoVs from the same genus, even the same subgenus, may recognize distinct receptors. For instance, unlike SARS-CoV and SARS-CoV-2 using ACE2 as receptor, betacoronaviruses MERS-CoV and MHV recognize receptors DPP4 and CEACAM1, respectively, whereas clade 2 sarbecoviruses were documented to utilize a yet unidentified receptor other than ACE2 for cellular entry.
Yes they are playing the same game as five years ago. We should ban ravel into the US from anyone from China or from a country dealing with them. Perhaps.
Posts
