One of the most critical requirements of the infection of the human immunodeficiency virus type 1 (HIV-1) is the interaction of its surface envelope glycoprotein gp120 with the cellular receptor CD4, which initiates virus entry to cells. Therefore, envelope glycoprotein gp120 has been validated as a potential target to develop HIV-1 entry inhibitors. Here we report the evaluation of a novel non-natural amino acid, termed 882376, reported earlier as a precursor of a CD4-mimetic miniprotein, as HIV-1 entry inhibitor. 882376 showed HIV-1 inhibitory activity against a large panel of primary isolates of different subtype. Moreover, genotyping of 882376 resistant HIV-1 virus revealed three amino acid substitutions in the gp120 including one in the CD4 binding site suggesting that this molecule may bind to gp120 and prevent its binding to CD4. Additional neutralization experiments indicate that 882376 is not active against mutant pseudoviruses carrying the amino acid substitutions S375H and S375Y located in the “Phe43 cavity” which is the major site of CD4 binding, suggesting that this compound may interfere with the interaction between gp120 and CD4. The unnatural amino acid, 882376, is expected to serve as a lead for further optimization to more potent HIV-1 entry inhibitors.

Since effective chemotherapeutics or preventive measures are still unavailable, finding feasible approaches against white spot syndrome virus (WSSV) has always been the vital subject in shrimp farming field. Envelope proteins are the ideal targets for antiviral strategies development due to their indispensable roles in virus entry, and inhibitory peptides targeting them have been proved to be promising in blocking virus infection. In this study, the Wimley-White interfacial hydrophobicity scale (WWIHS) in combination with known structural data was applied to identify potential inhibitory peptides that targeted the envelope protein VP28 of WSSV. Results showed that two potential inhibitory peptides were identified, one of which exhibited not only obvious antiviral activity, but also broad-spectrum antimicrobial activity. The inhibitory peptide identified here can serve as a lead compound for anti-WSSV strategies development.

No abstract