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Current Status and Progress in Developing Drugs to Treat Coronavirus Disease 2019 (COVID-19)

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Since first emerging in late 2019, the novel coronavirus known as SARS-CoV-2 has spread rapidly worldwide, causing a pandemic of coronavirus disease 2019 (COVID-19). While vaccines are helping to bring the pandemic under control, development of effective drug treatments remains an urgent public health priority. This article reviews the current status and progress of drug development research focused on treating COVID-19.

Repurposed Antivirals and Other Drugs

In the early stages of the pandemic before virus-specific therapies could be developed, clinicians and researchers turned to existing drugs that might have antiviral activity against SARS-CoV-2. Some of the most promising repurposed drugs evaluated have included:

- Remdesivir: An antiviral originally developed to treat Ebola virus, remdesivir interferes with viral RNA replication and was shown to modestly shorten recovery time in hospitalized COVID-19 patients in clinical trials. It was granted emergency use authorization by the FDA.

- Dexamethasone: A corticosteroid, dexamethasone demonstrated a mortality benefit in hospitalized patients requiring oxygen or mechanical ventilation in a large UK clinical trial. However, it is not recommended for non-hospitalized or mild disease cases.

- Convalescent plasma: Collected from recovered Coronavirus Treatment Drugs patients, convalescent plasma contains antibodies that may help the immune system fight infection. Data on effectiveness is limited and results have been inconsistent across studies.

- Hydroxychloroquine and chloroquine: These antimalarial drugs received significant attention early on but were found to have no benefit or possibly increase risks based on larger, higher quality clinical trials. Most major studies of them have now been discontinued.

Monoclonal Antibody Treatments

Another strategy involves development of laboratory-produced monoclonal antibody therapies targeting the SARS-CoV-2 virus. The goal is to generate antibodies that can block viral entry or replication. Some leading monoclonal antibody treatment candidates include:

- Bamlanivimab: Developed by Eli Lilly, bamlanivimab received emergency use authorization from the FDA in November 2020 based on an interim analysis finding it reduced COVID-19 related hospitalizations and ER visits in high-risk patients with mild-moderate disease.

- REGN-COV2: This combination monoclonal antibody cocktail from Regeneron was granted emergency authorization in November 2020 for non-hospitalized COVID-19 patients at high risk of severe illness. It was part of the treatment received by then-President Trump.

- Sotrovimab: Developed by GlaxoSmithKline and Vir Biotechnology, sotrovimab targets a conserved epitope on the SARS-CoV-2 spike protein and has demonstrated high in vitro potency against current variants of concern. In March 2021, it received emergency use authorization from the FDA based on interim clinical trial results.

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