A Novel Strategy for the Development of Vaccines for SARS-CoV-2 (COVID-19) and Other Viruses Using AI and Viral Shell Disorder

Abstract

A model that predicts levels of coronavirus (CoV) respiratory and fecal–oral transmission potentials based on the shell disorder has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Using primarily the PID of N, SARS-CoV-2 is grouped as having intermediate levels of both respiratory and fecal–oral transmission potentials. Related studies, using similar methodologies, have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and case-fatality rates of 0.5–5% and 10.9%, respectively. The underlying relationship between virulence and respiratory potentials has to do with the viral loads of vital organs and body fluids, respectively. Viruses can spread by respiratory means only if the viral loads in saliva and mucus exceed certain minima. Similarly, a patient is likelier to die when the viral load overwhelms vital organs. Greater disorder in inner shell proteins has been known to play important roles in the rapid replication of viruses by enhancing the efficiency pertaining to protein–protein/DNA/RNA/lipid bindings. This paper suggests a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells (N) of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore, this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its greater contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Computational, Experimental, and Clinical Evidence of a Specific but Peculiar Evolutionary Nature of (COVID-19) SARS-CoV-2

“…Both sequences and PONDR VLXT results were automatically added to a MySQL server using a JAVA program. 16 Measurements of sequence homology were obtained using BLASTP ( ). Phylogenetic trees were constructed using EMBI-EBI Clustal Omega ( ).…”

“…We first made the accurate prediction of the feasibility of a COVID-19 vaccine in a paper published in October 2020, months before the first COVID-19 vaccine was approved by the U.S. FDA. 16 , 17 , 54 …”

“… 17 , 18 This lead us to correctly foresee the successful development of effective vaccines for COVID-19 months before their approval by the U.S. Food and Drug Administration (FDA). 16 , 17 The model involves the use of AI to detect and calculate the levels of intrinsic disorder in query proteins. In 2014, there was a spinoff of this model that detected positive correlations between inner shell disorder and virulence among a variety of viruses, such as Ebola (EBOV) and Nipah (NiV) viruses.…”

Shell Disorder Analysis Suggests That Pangolins Offered a Window for a Silent Spread of an Attenuated SARS-CoV-2 Precursor among Humans

“…Later, another opportunity to test the model came, and this time it came in the form of the COVID-19 outbreak. Models suggested that the SARS-CoV-2 has to be in group B; i.e., a group with intermediate respiratory transmission, given its N PID of 48%. − Furthermore, something else strange and puzzling was seen in this virus: i.e., it has one of the hardest outer shells in the sizable sample of a wide variety of CoVs that we had analyzed . This could account for the high levels of the SARS-CoV-2 contagiousness, as a hard outer shell is likely to make the virus more resistant to the antimicrobial enzymes found in body fluids, such as saliva and mucus. , This should be manifested by higher viral load in the saliva and mucus.…”

Intrinsically Disordered Proteins: Perspective on COVID-19 Infection and Drug Discovery

“…Indeed, correlation has been confirmed between the virulence of various viruses and the percentage of intrinsic disorder of their M protein, with the less disordered viruses being more contagious. 105 …”