COVID-19, Influenza and RSV: Surveillance-informed prevention and treatment – Meeting report from an isirv-WHO virtual conference

Abstract

The International Society for Influenza and other Respiratory Virus Diseases (isirv) and the WHO held a joint virtual conference from 19th-21st October 2021. While there was a major focus on the global response to the SARS-CoV-2 pandemic, including antivirals, vaccines and surveillance strategies, papers were also presented on treatment and prevention of influenza and respiratory syncytial virus (RSV). Potential therapeutics for SARS-CoV-2 included host-targeted therapies baricitinib, a JAK inhibitor, tocilizumab, an IL-6R inhibitor, verdinexor and direct acting antivirals ensovibep, S-217622, AT-527, and monoclonal antibodies casirivimab and imdevimab, directed against the spike protein. Data from trials of nirsevimab, a monoclonal antibody with a prolonged half-life which binds to the RSV F-protein, and an Ad26.RSV pre-F vaccine were also presented. The expanded role of the WHO Global Influenza Surveillance and Response System to address the SARS-CoV-2 pandemic was also discussed. This report summarizes the oral presentations given at this meeting for the benefit of the broader medical and scientific community involved in surveillance, treatment and prevention of respiratory virus diseases.

Therapeutic efficacy of antibodies and antivirals against a SARS-CoV-2 Omicron variant

“…After establishing the in vitro sensitivity of the Omicron variants to antiviral compounds, we assessed their therapeutic e ciencies in hamsters infected with the Omicron variant (NC928). The dosage of compounds for hamsters was determined based on previous studies to evaluate the effect of molnupiravir and S-217622 against SARS-CoV-2 in the mouse model 18,19 . Hamsters intranasally infected with 10 3 PFU of virus were treated by oral gavage twice daily (at 12-h intervals) for 3 days with 1,000 mg/kg/day or with 120 mg/kg/day of molnupiravir and S-217622, respectively, beginning 24 h postinfection (Fig.…”

“…Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease 2019 (COVID- 19), continues to spread around the world and has caused 5.4 million deaths to date. The Omicron variant (B.1.1.529) of SARS-CoV-2 was detected in November 2021 in South Africa and has spread rapidly around the world.…”

First-generation oral antivirals against SARS-CoV-2

“…Table adapted from [ 44 ]. Antiviral agent Company Status RdRp Inhibitors Molnupiravir Merck & Co. Authorized for clinical use a GS-5245 (Remdesivir oral) Gilead/Jubilant Phase 1 [ 45 ] Prodrug of remdesivir parent compound (nucleoside GS-441524) ODBG-P-RVn University of California San Diego Preclinical [ 46 ] GS-621763 Gilead/Georgia State University Preclinical [ 47 ] M pro Inhibitors Nirmatrelvir/ritonavir Pfizer Authorized for clinical use a S-217622 Shionogi Phase 2/3 (Japan) [ [48] , [49] , [50] ] PBI-0451 Pardes Biosciences Phase 1 [ 51 ] EDP-235 Enanta Preclinical [ 52 , 53 ] a Several health authorities have authorized the emergency use of the compound. The list of countries that have authorized one compound or both drugs is subject to change and not listed.…”

A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-like Protease Inhibitor, in Japanese Patients With Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part

“…As the SARS-CoV-2 3CL protease is essential for processing viral complex proteins needed for viral replication (13), its inhibition by ensitrelvir is expected to prevent viral replication. Indeed, ensitrelvir has shown antiviral efficacy in both in vitro and in vivo animal studies (12, 14). Moreover, its safety, tolerability, and pharmacokinetic profile as single and multiple oral doses have been assessed in a phase 1 study (R. Shimizu, et al, unpublished data).…”