NeoCoV, a coronavirus strain related to MERS-CoV found in bats (NeoCoV is not a new variant of SARS-CoV-2, the human coronavirus strain responsible for COVID-19 pandemic) has been reported to be the first case of a MERS-CoV variant using ACE2. NeoCoV has potential of human emergence with both high fatality and transmission rate.
NeoCoV is a related strain to MERS-CoV that uses bat ACE 2 receptors for its entry and infection into bat cells. However, the strains of MERS-CoV uses DPP4 receptors for cellular entry. It is important to note that the NeoCoV is not a new variant of SARS-CoV-2 that has caused the world-wide pandemic since its emergence in November 2019.
This article shows that NeoCoV and its close relative PDF-2180-CoV is able to efficiently bind to ACE 2 receptors in bat, but bind less favourably to human ACE 2 receptors. Studies using cryo-electron microscopy revealed a distinct virus-ACE 2 binding surface in case of binding of NeoCoV and PDF-2180-CoV to ACE 2 receptors. A molecular determinant implicates Asp 338 residue, that prevents NeoCoV from binding to human ACE 2 receptor. In addition, a T510F mutation in the receptor binding motif of NeoCoV causes it to efficiently bind human ACE 2 receptor.
Given the high fatality rate of 35% associated with MERS-CoV related viruses derived from Beta CoV lineage, the NeoCoV could pose a potential threat to emergence of a high transmissible strain of NeoCoV and PDF-2180-CoV (upon gaining the T510F mutation due to antigenic drift) that can cause infection and mortality in humans, far worse than the current pandemic. Antigenic drift refers to random genetic mutations that caused changes in the protein structure, thereby altering the protein’s ability to bind to a particular receptor. In addition, the infection caused by the T510F mutation of NeoCoV, could not be cross-neutralized by antibodies targeting SARS-CoV-2 or MERS-CoV.
The entire global community hopes that the mutation in NeoCoV and PDF-2180-CoV that causes it to efficiently bind to human ACE 2 receptor, remains a laboratory study to understand the virulence of these viruses, and it doesn’t become a case of zoonotic transmission from bats to humans, creating another worldwide chaos.
Yan H., et al 2022. Close relatives of MERS-CoV in bats use ACE2 as their functional receptors. Preprint bioRxiv. Posted 25 January 2022. DOI: https://doi.org/10.1101/2022.01.24.477490