Regdanvimab for COVID-19

Abstract Background Regdanvimab (CT-P59) is a monoclonal antibody with neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report on part 1 of a 2-part randomized, placebo-controlled, double-blind study for mild-to-moderate patients with coronavirus disease 2019 (COVID-19). Methods Outpatients with mild-to-moderate COVID-19 received a single dose of regdanvimab 40 mg/kg (n=100), regdanvimab 80 mg/kg (n=103), or placebo (n=104). Primary endpoints were time to negative conversion of SARS-CoV-2 from nasopharyngeal swab based on quantitative reverse transcription polymerase chain reaction (RT-qPCR) up to day 28 and time to clinical recovery up to day 14. Secondary endpoints included the proportion of patients requiring hospitalization, oxygen therapy, or mortality due to COVID-19. Results Median (95% confidence interval [CI]) time to negative conversion of RT-qPCR was 12.8 days (9.0–12.9) with regdanvimab 40 mg/kg, 11.9 days (8.9–12.9) with regdanvimab 80 mg/kg, and 12.9 days (12.7–13.9) with placebo. Median (95% CI) time to clinical recovery was 5.3 days (4.0–6.8) with regdanvimab 40 mg/kg, 6.2 days (5.5–7.9) with regdanvimab 80 mg/kg, and 8.8 days (6.8–11.6) with placebo. The proportion (95% CI) of patients requiring hospitalization or oxygen therapy was lower with regdanvimab 40 mg/kg (4.0% [1.6–9.8]) and regdanvimab 80 mg/kg (4.9% [2.1–10.9]) versus placebo (8.7% [4.6–15.6). No serious treatment-emergent adverse events or deaths occurred. Conclusions Regdanvimab showed a trend toward a minor decrease in time to negative conversion of RT-qPCR results compared with placebo and reduced the need for hospitalization and oxygen therapy in patients with mild-to-moderate COVID-19.

Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19.

By January of 2023, the COVID-19 pandemic had led to a reported total of 6,700,883 deaths and 662,631,114 cases worldwide. To date, there have been no effective therapies or standardized treatment schemes for this disease; therefore, the search for effective prophylactic and therapeutic strategies is a primary goal that must be addressed. This review aims to provide an analysis of the most efficient and promising therapies and drugs for the prevention and treatment of severe COVID-19, comparing their degree of success, scope, and limitations, with the aim of providing support to health professionals in choosing the best pharmacological approach. An investigation of the most promising and effective treatments against COVID-19 that are currently available was carried out by employing search terms including “Convalescent plasma therapy in COVID-19” or “Viral polymerase inhibitors” and “COVID-19” in the Clinicaltrials.gov and PubMed databases. From the current perspective and with the information available from the various clinical trials assessing the efficacy of different therapeutic options, we conclude that it is necessary to standardize certain variables—such as the viral clearance time, biomarkers associated with severity, hospital stay, requirement of invasive mechanical ventilation, and mortality rate—in order to facilitate verification of the efficacy of such treatments and to better assess the repeatability of the most effective and promising results.

Viruses with rapid replication and easy mutation can become resistant to antiviral drug treatment. With novel viral infections emerging, such as the recent COVID-19 pandemic, novel antiviral therapies are urgently needed. Antiviral proteins, such as interferon, have been used for treating chronic hepatitis C infections for decades. Natural-origin antimicrobial peptides, such as defensins, have also been identified as possessing antiviral activities, including direct antiviral effects and the ability to induce indirect immune responses to viruses. To promote the development of antiviral drugs, we constructed a data repository of antiviral peptides and proteins (DRAVP). The database provides general information, antiviral activity, structure information, physicochemical information, and literature information for peptides and proteins. Because most of the proteins and peptides lack experimentally determined structures, AlphaFold was used to predict each antiviral peptide’s structure. A free website for users (http://dravp.cpu-bioinfor.org/, accessed on 30 August 2022) was constructed to facilitate data retrieval and sequence analysis. Additionally, all the data can be accessed from the web interface. The DRAVP database aims to be a useful resource for developing antiviral drugs.