Computational Evaluation of the Inhibition Efficacies of HIV Antivirals on SARS-CoV-2 (COVID-19) Protease and Identification of 3D Pharmacophore and Hit Compounds

Table 1

Binding score of anti-HIV drugs on the SARS-CoV-2 protease and types of interactions.

Anti-HIV drugs	Binding energy (kcal/mol)	Interactions	Amino acid residues
Atazanavir	−6.4	H-bond	Glu166-2(HB), Gly143(HB), Gly170(NC), Gln189-2(NC), Asn142(NC)
		π type	His41(π^+), Cys145(πS), Cys145(π−π), Leu27(π-R)
		van der Waals	Leu167, His164, His163, Ser144, His172
Darunavir	−7.5	H-bond	His41(HB), Leu141(HB), Gly143(HB), His164(NC), Gln189(NC)
		π and R type	His41-3(π-R)Met49-2(R)
		van der Waals	Arg188, Cys145, His163
		Unfavourable	Ser144, Thr25
Amprenavir	−7.4	H-bond	Thr24(HB), His41(HB), Gly143(HB), Gly143(NC), His41(NC)
		π and R type	Leu141(π-stack), His41(π-S), Met165(R)
		van der Waals	Asn142
Saquinavir	−9.0	H-bond	Glu166(HB), His41(HB), His164(HB), Gln189(HB), Gln189(NC), Met165(NC)
		π and R type	Pro168(π-R), His163(π-R), Cys145-2(π-R), Met49(π-R)
		van der Waals	Phe140, His172, Leu27, Phe181, Arg188, Gln192
Lopinavir	−8.1	H-bond	Glu166(HB), Gln189(HB), Met165(NC)
		π and R type	His41(π-R), Met49(π-R), Met165(π-S), His41(π-stack), Leu27(R)
		van der Waals	Phe140,Cys145, His163, His164, His172
Ritonavir	−7.2	H-bond	Gly143(HB), Gln189(HB), Asn142(NC), Met165(NC), Glu166(NC), Glu189(NC), Thr190(NC), Thr26(NC),
		π and R type	Met49(π-R), Pro168(π-R), Met165(π-S), His41(π^+), Glu166(π^−), Thr25(π-σ), Met49(R)
		van der Waals	Leu27, Thr45, Ser46, Tyr54, Phe40, Cys145, Asp187, Arg188
Nelfinavir	−8.2	H-bond	Gly143-2(HB)
		π and R type	His41(π^+), Leu141(π-stack), Met49(π-R), Met165(R)
		van der Waals	Asn142
Indinavir	−8.1	H-bond	Glu166(HB), Gln143(NC), Gln189(NC)
		π and R type	Leu141(π-stack), Thr190(π-stack), Ala191(π-R)
		van der Waals	Asn142

HB: conventional H-bond; NC: nonconventional H-bond. π⁺ = π-cation, π⁻ = π-anion, π-R = π-alkyl, π-S = π-sulphur, and π-stack = π-stacking interactions. R = alkyl.