| Autor: |
Mtambo SE; Drug Research and Innovation Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa., Ugbaja SC; Drug Research and Innovation Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa., Mushebenge AG; Drug Research and Innovation Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa., Abubakar BH; Renewable Energy Programme, Federal Ministry of Environment, 444 Aguiyi Ironsi Way, Maitama, Abuja 904101, Nigeria., Ntuli ML; Department of Mathematics, Faculty of Applied Science, Durban University of Technology, Durban 4001, South Africa., Kumalo HM; Drug Research and Innovation Unit, Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4000, South Africa. |
| Abstrakt: |
The H7N9 virus attaches itself to the human cell receptor protein containing the polysaccharide that terminates with sialic acid. The mutation of neuraminidase at residue E119 has been explored experimentally. However, there is no adequate information on the substitution with E119V in peramivir at the intermolecular level. Therefore, a good knowledge of the interatomic interactions is a prerequisite in understanding its transmission mode and subsequent effective inhibitions of the sialic acid receptor cleavage by neuraminidase. Herein, we investigated the mechanism and dynamism on the susceptibility of the E119V mutation on the peramivir-neuraminidase complex relative to the wildtype complex at the intermolecular level. This study aims to investigate the impact of the 119V substitution on the neuraminidase-peramivir complex and unveil the residues responsible for the complex conformations. We employed molecular dynamic (MD) simulations and extensive post-MD analyses in the study. These extensive computational investigations were carried out on the wildtype and the E119V mutant complex of the protein for holistic insights in unveiling the effects of this mutation on the binding affinity and the conformational terrain of peramivir-neuraminidase E119V mutation. The calculated total binding energy (ΔG bind ) for the peramivir wildtype is -49.09 ± 0.13 kcal/mol, while the E119V mutant is -58.55 ± 0.15 kcal/mol. The increase in binding energy (9.46 kcal/mol) is consistent with other post-MD analyses results, confirming that E119V substitution confers a higher degree of stability on the protein complex. This study promises to proffer contributory insight and additional knowledge that would enhance future drug designs and help in the fight targeted at controlling the avian influenza H7N9 virus. Therefore, we suggest that experimentalists collaborate with computational chemists for all investigations of this topic, as we have done in our previous studies. |
