Ribosomal Proteins Homologies and Methylation of Mitoribosome by Corona Virus Nsp9, Nsp10 and Previously Described Nsp13-16 Proteins Suggested Their Roles in the Inhibition of Host Protein Synthesis: Discovery of New Therapeutic Targets against Corona Virus Infections<strong> </strong>

Abstract

Multi-Alignment method coupled with phylogenetic analysis we disclosed the Nsp9 and Nsp10 non-structural proteins of Corona Virus as rRNA RlmH/K methyltransferases with similarities with bin recombinase and int-core integrase fold. Further, Nsp9 has similarities to S8 ribosomal protein and Nap10 has similarity to S10 ribosomal protein. Previously, we showed Nsp13, Nsp14, Nsp15 and Nsp16 are also different types of rRNA RlmE/N and Cfr-like methyltransferases-ribonuclease with RNA helicase domains. Two domains of Nsp13 astonishingly have similarities to ribosomal proteins L6 and L9. Taken together, Nsp9/10 and Nsp13-16 proteins could mimic host ribosome assembly and also could methylate rRNA of mitobibosome preventing mitochondrial protein synthesis and oxidative phosphorylation. Low ATP synthesis causes lowering blood pressure following coma but very ATP concentration (1-10nM) surely induces platelets aggregation through vWA, collagen and GpIIb/IIIa proteins followed by fibrin formation and blood clotting as recently have seen in the lung of many Corona virus infected patients. We have also postulated that two polyproteins itself resemble like 28S and 38S mitoribosome subunits and compete with rRNAs inhibiting the ribosome turnover and new protein synthesis due to their similarities with many ribosomal proteins. Such finding may be valuable in computer-based novel drug design against Corona virus.

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“…Recently, many laboratories worldwide engaged with yeast cells-expressed protein vaccine based on altered spike protein of Omicron corona viruses. However, adenovector based DNA-vaccine and mRNA vaccine were found good based on spike protein [59,60] as well as other proteins like RNA topoisomerase (nsp2) and uridine methyl transferases (nsp16) [9,18]. The co-infection of multidrug resistant bacteria in patients were reported and thus infections were very serious as most antibiotics failed to cure such pan-drugs resistant infections [61,62].…”

“…Most astonishing fact was large polyprotein (7096 AAs) synthesis in the infected cells and such proteins were proteolytically cleaved into 16 polypeptides with important biological functions [6]. The Nsp1 protein is 180aa (regulatory factor), nsp2 is 638aa (RNA topoisomerase), nsp3 is ~1945aa (C3 protease), nsp4 is 500aa (membrane factor), nsp5 is ~305aa (C5 protease), nsp6 is 290aa (membrane factor), nsp7 is 183aa (accessory protein to replication), nsp8 is 198aa (accessory protein to replication), nsp9 is 113aa (RNA binding factor), nsp10 is 139aa (RNA binding factor), nsp11 is only 13aa (unknown function), nsp12 is 918aa (RNA-dependent RNA polymerase), nsp13 is 601aa (RNA helicase-capping methyltransferase), nsp14 is 527aa (exoribonuclease-methyltransferase) , nsp15 is 346aa (endoribonuclease-recombinase), nsp16 is 298aa (2'-O Uridine rRNA methyltransferase) [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. On the country, structural spike protein is 1273aa long and other structural proteins (M, N, E) of corona virus are relatively very small [24][25][26][27][28][29].…”