Raju Hazari

Raju Hazari, Parimal Pal Chaudhuri

Significantly higher transmissibility of SARS CoV-2 (2019) compared to SARS CoV (2003) can be attributed to mutations of structural proteins (Spike S, Nucleocapsid N, Membrane M, and Envelope E) and the role played by non-structural proteins (nsps) and accessory proteins (ORFs) for viral replication, assembly and shedding. The non-structural proteins (nsps) avail host protein synthesis machinery to initiate viral replication, along with neutralization of host immune defense. The key protein out of the 16 nsps, is the non-structural protein nsp1, also known as the leader protein. Nsp1 leads the process of hijacking host resources by blocking host translation. This paper concentrates on the analysis of nsps of SARS covid (CoV-2, CoV) and MERS covid based on Cellular Automata enhanced Machine Learning (CAML) model developed for study of biological strings. This computational model compares deviation of structure - function of CoV-2 from that of CoV employing CAML model parameters derived out of CA evolution of amino acid chains of nsps. This comparative analysis points to - (i) higher transmissibility of CoV-2 compared to CoV for major nsps, and (ii) deviation of MERS covid from SARS CoV in respect of virulence and pathogenesis. A Machine Learning (ML) framework has been designed to map the CAML model parameters to the physical domain features reported in in-vitro/in-vivo/in-silico experimental studies. The ML framework enables us to learn the permissible range of model parameters derived out of mutational study of sixteen nsps of three viruses.

Raju Hazari, P Pal Chaudhuri

The reason of significantly higher transmissibility of SARS Covid (2019 CoV-2) compared to SARS Covid (2003 CoV) and MERS Covid (2012 MERS) can be attributed to mutations reported in structural proteins, and the role played by non-structural proteins (nsps) and accessory proteins (ORFs) for viral replication, assembly, and shedding. Envelope protein E is one of the four structural proteins of minimum length. Recent studies have confirmed critical role played by the envelope protein in the viral life cycle including assembly of virion exported from infected cell for its transmission. However, the determinants of the highly complex viral - host interactions of envelope protein, particularly with host Golgi complex, have not been adequately characterized. CoV-2 and CoV Envelope proteins of length 75 and 76 amino acids differ in four amino acid locations. The additional amino acid Gly (G) at location 70 makes CoV length 76. The amino acid pair EG at location 69-70 of CoV in place of amino acid R in location 69 of CoV-2, has been identified as a major determining factor in the current investigation. This paper concentrates on the design of computational model to compare the structure/function of wild and mutants of CoV-2 with wild and mutants of CoV in the functionally important region of the protein chain pair. We hypothesize that differences of CAML model parameter of CoV-2 and CoV characterize the deviation in structure and function of envelope proteins in respect of interaction of virus with host Golgi complex; and this difference gets reflected in the difference of their transmissibility. The hypothesis has been validated from single point mutational study on- (i) human HBB beta-globin hemoglobin protein associated with sickle cell anemia, (ii) mutants of envelope protein of Covid-2 infected patients reported in recent publications.