| Popis: |
A study of some commonly used anti-viral nucleotide analogs using quantum mechanical methods has been carried out. Specifically the binding of nucleoside triphosphates (NTPs derived from IDX-184, Ribavirin, Sofosbuvir, Remdesivir, Molnupiravir, Favipiravir, AZT, Alovudine, and some natural NTPs etc) base paired with nucleosides (cytosine, guanine, adenine) has been studied since the rate-limiting step of RNA synthesis involves nucleoside analog triphosphates in the formation of the RNA/RdRp complex. It is shown that the location of the frontier orbitals and their HOMO-LUMO (HL) gaps can be used to predict the stability of the nucleotide analogs as shown in IDX-184, AZT, Alovudine and Sofosbuvir etc, rather than notions of steric effects reported in the literature. The major effect determining stabilities are electrostatic effects from the orientation of the anionic TP groups when the nucleotide analogs hydrogen bond with base pairs. The HL gaps and energies of the first excited states of NTP-nucleobase complexes can show which bases form more stable complexes, and which tautomeric form of the NTPs form the more stable complexes. The influence of how various substituents on the ribose (ribofuranose) ring influence the interaction of nucleotide analogs (eg IDX-184, Ribavirin, Sofosbuvir, Remdesivir, Molnupiravir, Favipiravir, AZT, Alovudine) with RdRp is also demonstrated. It was shown that Sofosbuvir has unique features amongst these drugs. These factors can be useful in design of more effective anti-viral drugs. |
