Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Antiviral Activity of N-ω-Chloroacetyl-L-Ornithine on In Vitro Replication of the Chikungunya Virus

Version 1 : Received: 11 December 2020 / Approved: 14 December 2020 / Online: 14 December 2020 (12:34:24 CET)

How to cite: Luna-Rojas, L.; Avila-Trejo, A.M.; Alcantara-Farfán, V.; Rodriguez-Paez, L.I.; Pastor-Alonso, M.O.; Posadas-Mondragón, A.; Aguilar-Faisal, J.L. Antiviral Activity of N-ω-Chloroacetyl-L-Ornithine on In Vitro Replication of the Chikungunya Virus. Preprints 2020, 2020120328 (doi: 10.20944/preprints202012.0328.v1). Luna-Rojas, L.; Avila-Trejo, A.M.; Alcantara-Farfán, V.; Rodriguez-Paez, L.I.; Pastor-Alonso, M.O.; Posadas-Mondragón, A.; Aguilar-Faisal, J.L. Antiviral Activity of N-ω-Chloroacetyl-L-Ornithine on In Vitro Replication of the Chikungunya Virus. Preprints 2020, 2020120328 (doi: 10.20944/preprints202012.0328.v1).

Abstract

The infections caused by Chikungunya virus (CHIKV), genus Alphavirus, have become a health problem around the world, due to this virus’s widespread occurrence and high morbidity rate and the absence of vaccines or antiviral drugs. In this study, we analyzed a competitive inhibitor of ornithine decarboxylase—an enzyme that is key in the biosynthesis of polyamines (PAs), N-ω-chloroacetyl-L-ornithine (NCAO), which is a possible inhibitor of CHIKV replication because intracellular polyamines participate in the in vitro transcription and translation of CHIKV. NCAO does not have any cytotoxic effect on C6/36 cells even at 1000 μM at 72 h post-exposure. However, in Vero cells, a cytotoxic effect was present above 380 μM at 48 h post-exposure, which was considered when determining the inhibitory effect on viral replication. In this work, we demonstrate that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p <0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though mainly spermidines and spermines are present in infected cells. NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero and C6/36 cells, suggesting that this compound is a possible antiviral for CHIKV infections.

Subject Areas

Chikungunya replication; antiviral; N-ω-Chloroacetyl-L-Ornithine; polyamines

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