Antiviral activity of new organophosphorus compounds in vitro

Background. The search for new antiviral compounds is a priority due to growing pathogen resistance. Phosphonates, characterized by a stable carbon–phosphorus bond, represent a promising class of organophosphorus derivatives. However, data on the antiviral activity of newly synthesized phosphonates against alphaherpesviruses remain limited.

Objective. To evaluate the cytotoxicity and antiviral activity of five novel phosphonates (SAN-1, SAN-2, SAN-3, SAN-4, and DII-C2) against pseudorabies virus (SuHV-1) in Vero cell culture.

Methods. The infectious virus titer was determined using the Reed–Muench method. Cytotoxicity was assessed by visual microscopy and quantitative MTT assay after 72 h of incubation. Antiviral activity was evaluated by measuring the reduction of virus-induced cytopathic effect (CPE) and calculating virus titer reduction (log₁₀ TCID₅₀/mL) using the Spearman–Kärber method. All compounds were tested at a concentration range of 100–0.0001 μg/mL.

Results. The SuHV-1 virus titer was 7.08±0.17 lg TCID₅₀/mL, confirming its suitability for screening. None of the tested phosphonates exhibited cytotoxicity at concentrations up to 100 μg/mL, with cell viability ranging from 92 to 96 % relative to untreated controls. Four compounds (SAN 2, SAN 3, SAN 4, and DII C2) showed pronounced antiviral activity, providing 72–82.5 % cell protection and reducing virus titers by 2.25–2.63 log₁₀. SAN 1 demonstrated weak activity (20 % protection). The highest efficacy was observed for DII C2 (82.5 % protection).

Conclusion. SAN 2, SAN 3, SAN 4, and DII C2 exhibit low cytotoxicity and significant anti SuHV 1 activity in vitro. These compounds are promising candidates for further preclinical studies as potential antiviral agents.

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