SARS-CoV-2 Origin

SARS-CoV-2 ORIGIN

Covid-19 was reported in Wuhan, Hubei Province, China at the end of 2019. Covid-19 cause by infection of novel coronavirus SARS-CoV-2. Infection with this virus are now globaly widespread and as of 30 June 2020, total of 10,302,867 cases have been confirmed with 505,518 deaths. In the midst of the global COVID-19 public-health emergency, it is reasonable to wonder why the origins of the pandemic matter. Yet, until now there has been considerable debate on the origin of the causative virus.

SARS-CoV-2 is the seventh coronavirus known to infect humans; SARS-CoV, MERS-CoV and SARS-CoV-2 can cause severe disease, whereas HKU1, NL63, OC43 and 229E are associated with mild symptoms. The membrane of coronaviruses harbors Spike(S)-glycoprotein which is essential for entry of virus particles into the cell. The S-glycoprotein contains two functional domains: a receptor binding domain (RBD/S1), and a second domain (S2) which contains sequences that mediate fusion of the viral and cell membranes. The S-glycoprotein must be cleaved by cell proteases to enable exposure of the fusion sequences for cell entry. Comparison of coronaviruses genom identifies two notable genomic features of S glycoprotein of SARS-CoV-2: (i) SARS-CoV-2 appears to be optimized for binding to the human receptor ACE2; and (ii) the S-glikoprotein of SARS-CoV-2 has a functional polybasic (furin) cleavage site at the S1–S2 junction.

The RBD in S- glycoprotein is the most variable part of the coronavirus genome. Given the similarity of SARS-CoV-2 to bat coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor. Although a betacoronavirus RaTG13 genom sampled from a Rhinolophus affinis bat is 96% identical overall to SARS-CoV-2 genom, its S-glycoprotein diverges in the RBD. Malayan pangolins (Manis javanica) contain betacoronaviruses doesn’t has a similar genom with SARS-CoV-2 but it has a similar RBD that exhibit strong similarity (97%) to SARS-CoV-2 RBD. On the basis of structural studies and biochemical experiments, SARS-CoV-2 seems to have an RBD that binds with high affinity to ACE2 from humans and other species with high receptor homology. But computational analyses predict that the interaction of SARS-CoV-2 RBD with ACE2 is not ideal and its sequence is different from those shown in SARS-CoV to be optimal for receptor binding. The RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution that different from those previously predicted. If genetic manipulation had been performed, one of the several optimation available would probably have been used. The high-affinity binding of the SARS-CoV-2 RBD to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of genetic manipulation.

SARS-CoV-2 has a polybasic cleavage site (furin) at the S1-S2 junction. This site  allows effective cleavage by furin proteases that abundant in human respiratory tract. This site has a role in determining viral infectivity and host range. There is still need a further research to determine how polybasic cleavage site within the S glycoprotein of SARS-CoV-2 is actually cleaved. Neither the bat betacoronaviruses nor the pangolin betacoronaviruses sampled thus far have polybasic cleavage sites but another human betacoronaviruses, including HKU1 (lineage A), have those sites. The polybasic cleavage site might have been acquired by recombination with another virus possessing that site. Mutations, insertions and deletions can occur near the S1–S2 junction of SARS-CoV-2, which shows that the polybasic cleavage site can arise by a natural evolutionary process.

For a precursor virus SARS-CoV-2 could acquire both the polybasic cleavage site and mutations in the RBD suitable for binding to human ACE2, an animal host would probably have to have a high population density (to allow natural selection to proceed efficiently) and an ACE2-encoding gene that is similar to the human ortholog. With genom almost identical with betacoranvirus from bat, an RBD that almost identical with pangolin betacoronavirus and polybasic cleavage site similar in human betacoronavirus (HKU)1 strongly suggest that the SARS-CoV-2 spike protein optimized for binding to human-like ACE2  is occur in nature as result of natural selection. In conclusion, I want to use some modified quote from famous film “Contagion” in which some General asked Director of CDC is there any chance someone weaponized the virus and use it as bioweapon. The Director of CDC answer can resume all the conclusion from this articel : “Someone doesn’t have to weaponize the coronavirus, the nature itself are doing that”.