Why doesn't Ebola virus cause pandemics like SARS-CoV-2?

Ebola virus is among the most dangerous, contagious and deadly etiological causes of viral diseases. However, Ebola virus has never extensively spread in human population and never have led to a pandemic. Why? The mechanistic biophysical model revealing the biothermodynamic background of virus-host interaction) could help us to understand pathogenesis of Ebola virus disease (earlier known as the Ebola hemorrhagic fever). In this paper for the first time the empirical formula, thermodynamic properties of biosynthesis (including the driving force of virus multiplication in the susceptible host), binding constant and thermodynamic properties of binding are reported. Thermodynamic data for Ebola virus were compared with data for SARS-CoV-2 to explain why SARS-CoV-2 has caused a pandemic, while Ebola remains on local epidemic level. The empirical formula of the Ebola virus was found to be CH1.569O0.3281N0.2786P0.00173S0.00258. Standard Gibbs energy of biosynthesis of the Ebola virus nucleocapsid is -151.59 kJ/C-mol.

Absolute binding free energies of the antiviral peptide ATN-161 with protein targets of SARS-CoV-2.

The interactions of the antiviral pentapeptide ATN-161 with the closed and open conformations of the α5ß1 integrin, the SARS-CoV-2 major protease, and the omicron variant spike protein complexed with hACE2 were studied using molecular docking and molecular dynamics simulation. Molecular docking was performed to obtain ATN-161 binding poses with these studied protein targets. Subsequently, molecular dynamics simulations were performed to verify the ligand stability at the binding site of each protein target. Pulling simulations, umbrella sampling, and weighted histogram analysis method were used to obtain the potential of mean force of each system and calculate the Gibbs free energy of binding for the ATN-161 peptide in each binding site of these protein targets. The results showed that ATN-161 binds to α5ß1 integrin in its active and inactive form, binds weakly to the omicron variant spike protein complexed with hACE2, and strongly binds to the main protease target.Communicated by Ramaswamy H. Sarma.

Absolute binding free energies of mucroporin and its analog mucroporin-M1 with the heptad repeat 1 domain and RNA-dependent RNA polymerase of SARS-CoV-2.

The peptide Mucroporin and its analog Mucroporin-M1 were studied using the molecular docking and molecular dynamics simulation of their complexation with two protein targets, the Heptad Repeat 1 (HR1) domain and RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2. The molecular docking of the peptide-protein complexes was performed using the glowworm swarm optimization algorithm. The lowest energy poses were submitted to molecular dynamics simulation. Then, the binding free energies of Mucroporin and its analog Mucroporin-M1 with these two protein targets were calculated using the Multistate Bennett Acceptance Ratio (MBAR) method. It was verified that the peptides/HR1 domain complex showed stability in the interaction site determined by molecular docking. It was also found that Mucroporin-M1 has a much higher affinity than Mucroporin to the HR1 protein target. The peptides showed similar stability and affinity at the NTP binding site in the RdRp protein. Additional experimental studies are needed to confirm the antiviral activity of Mucroporin-M1 and a possible mechanism of action against SARS-CoV-2. However, here we indicate that Mucroporin-M1 may have potential antiviral activity against the HR1 domain with the possibility for further peptide optimization.Communicated by Ramaswamy H. Sarma.

Strain wars 5: Gibbs energies of binding of BA.1 through BA.4 variants of SARS-CoV-2.

This paper reports, for the first time, standard Gibbs energies of binding of the BA.1, BA.2, BA.3, BA.2.13, BA.2.12.1 and BA.4 Omicron variants of SARS-CoV-2, to the Human ACE2 receptor. Variants BA.1 through BA.3 exhibit a trend of decreasing standard Gibbs energy of binding and hence increased infectivity. The BA.4 variant exhibits a less negative standard Gibbs energy of binding, but also more efficient evasion of the immune response. Therefore, it was concluded that all the analyzed strains evolve in accordance with expectations of the theory of evolution, albeit using different strategies.