Virtual screening identified compounds that bind to cyclin dependent kinase 2 and prevent herpes simplex virus type 1 replication and reactivation in neurons.

This study identified compounds that dock to a model of cyclin dependent kinase 2 (CDK2), a cellular enzyme required for efficient HSV-1 replication, and have anti-HSV-1 activity. Compounds obtained from virtual screening by Pharmit were filtered in FAFDrugs4 for good pharmacokinetic and toxicological profiles and submitted to molecular docking on CDK2 using Autodock Vina. The six most promising compounds were evaluated for inhibiting lytic replication of HSV-1 wild-type and ACV-resistant strains on human fibroblasts. The compounds were also assayed for cytotoxicity. Compounds 1, 2 and 3 showed antiviral activity with EC50s (50% of effective drug concentration) of 32, 29 and 64 μM and CC50s (50% of cytotoxic concentration) of 159, 1410 and 2044 μM, respectively. Compounds 1 and 2 were also active against ACV resistant strains and compound 3 inhibited the reactivation of HSV-1 in neurons, which is an important finding to guide drug design of new anti-HSV-1 antivirals with different modes of action. These compounds are promising candidates for optimization into more potent agents to treat HSV-1 infections and recurrences. PMID: 31634495 [PubMed - as supplied by publisher]
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research