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Dear Editor,
The partial accomplishment (or partial failure) of Remdesivir emphasizes the need for other therapeutic approaches that might complement this otherwise useful drug. We would like to focus on an underrated viral product. SARS-Cov-2’s ORF3a gene encodes an accessory protein, termed viroporin, expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment. Viroporins, well-studied in SARS-Cov, form multimeric complexes that act as ion channels (Minakshi et al., 2014; Ding et al., 2017; Schoeman and Fielding, 2019;). Apart from regulating virus release from infected cells, viroporins also trigger abnormal immunological host responses, activating the NLRP3 inflammasome and pro-IL-1β gene transcription/protein maturation through NF-κB (Siu et al., 2019; Chen and Li, 2020; Li et al., 2020). Further, the ORF3a gene displays rapid accumulation of non-synonymous mutations, with a possible impact on B-cell like epitope formation (Issa et al., 2020; Wang et al., 2020). It is straightforward to hypothesize that this underrated extra-virionic component could stand for a feasible therapeutic target for neutralizing monoclonal antibodies. Positive responses could be achieved against the two most dangerous effects of COVID-19 infection: indeed, viroporins are implicated both in host cell apoptosis and proinflammatory cytokines storm.
Gennaro D'Amato
Division of Respiratory and Allergic Diseases, Department of Chest Diseases, High Specialty A. Cardarelli Hospital, Napoli, Italy
Medical School of Specialization in Respiratory Diseases, University on Naples Federico II. gdamatomail@gmail.com
SARS-CoV-2 VIROPORIN: A BEHIND THE SCENES THERAPEUTIC TARGET
Dear Editor,
The partial accomplishment (or partial failure) of Remdesivir emphasizes the need for other therapeutic approaches that might complement this otherwise useful drug. We would like to focus on an underrated viral product. SARS-Cov-2’s ORF3a gene encodes an accessory protein, termed viroporin, expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment. Viroporins, well-studied in SARS-Cov, form multimeric complexes that act as ion channels (Minakshi et al., 2014; Ding et al., 2017; Schoeman and Fielding, 2019;). Apart from regulating virus release from infected cells, viroporins also trigger abnormal immunological host responses, activating the NLRP3 inflammasome and pro-IL-1β gene transcription/protein maturation through NF-κB (Siu et al., 2019; Chen and Li, 2020; Li et al., 2020). Further, the ORF3a gene displays rapid accumulation of non-synonymous mutations, with a possible impact on B-cell like epitope formation (Issa et al., 2020; Wang et al., 2020). It is straightforward to hypothesize that this underrated extra-virionic component could stand for a feasible therapeutic target for neutralizing monoclonal antibodies. Positive responses could be achieved against the two most dangerous effects of COVID-19 infection: indeed, viroporins are implicated both in host cell apoptosis and proinflammatory cytokines storm.
Arturo Tozzi
Center for Nonlinear Science, Department of Physics, University of North Texas, Denton, Texas, USA
tozziarturo@libero.it
Arturo.Tozzi@unt.edu
Gennaro D'Amato
Division of Respiratory and Allergic Diseases, Department of Chest Diseases, High Specialty A. Cardarelli Hospital, Napoli, Italy
Medical School of Specialization in Respiratory Diseases, University on Naples Federico II.
gdamatomail@gmail.com
Competing interests: No competing interests