PMID- 38140601 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20231225 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 15 IP - 12 DP - 2023 Nov 30 TI - The Antiviral Effect of Berdazimer Sodium on Molluscum Contagiosum Virus Using a Novel In Vitro Methodology. LID - 10.3390/v15122360 [doi] LID - 2360 AB - Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication. FAU - Ward, Brian M AU - Ward BM AD - Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA. FAU - Riccio, Daniel A AU - Riccio DA AUID- ORCID: 0009-0001-4255-4306 AD - Novan, Durham, NC 27703, USA. FAU - Cartwright, Martina AU - Cartwright M AUID- ORCID: 0000-0001-7207-2810 AD - Novan, Durham, NC 27703, USA. FAU - Maeda-Chubachi, Tomoko AU - Maeda-Chubachi T AUID- ORCID: 0000-0002-3614-1505 AD - Novan, Durham, NC 27703, USA. LA - eng PT - Journal Article DEP - 20231130 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - ORT9SID4QY (berdazimer sodium) RN - 0 (Siloxanes) RN - 0 (Antiviral Agents) SB - IM MH - United States MH - Child MH - Humans MH - *Molluscum contagiosum virus/genetics MH - *Molluscum Contagiosum/drug therapy MH - Siloxanes/metabolism MH - Antiviral Agents/pharmacology/metabolism PMC - PMC10747301 OTO - NOTNLM OT - berdazimer sodium OT - mechanism of action OT - molluscum contagiosum OT - molluscum contagiosum virus OT - nitric oxide COIS- B.M.W. received research funding for this study from Novan; D.A.R., M.C. and T.M.-C. are employees of Novan and receive a salary and stock or stock options. EDAT- 2023/12/23 12:44 MHDA- 2023/12/25 06:43 PMCR- 2023/11/30 CRDT- 2023/12/23 01:29 PHST- 2023/10/04 00:00 [received] PHST- 2023/11/23 00:00 [revised] PHST- 2023/11/28 00:00 [accepted] PHST- 2023/12/25 06:43 [medline] PHST- 2023/12/23 12:44 [pubmed] PHST- 2023/12/23 01:29 [entrez] PHST- 2023/11/30 00:00 [pmc-release] AID - v15122360 [pii] AID - viruses-15-02360 [pii] AID - 10.3390/v15122360 [doi] PST - epublish SO - Viruses. 2023 Nov 30;15(12):2360. doi: 10.3390/v15122360.