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Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Therapeutics for COVID-19
Sima S Toussi1, Jennifer L Hammond2, Brian S Gerstenberger3
1Pfizer, Pearl River, NY, USA.
Abstract:
Vaccines and monoclonal antibody treatments to prevent severe coronavirus disease 2019 (COVID-19) illness were available within a year of the pandemic being declared but there remained an urgent need for therapeutics to treat patients who were not vaccinated, were immunocompromised or whose vaccine immunity had waned. Initial results for investigational therapies were mixed. AT-527, a repurposed nucleoside inhibitor for hepatitis C virus, enabled viral load reduction in a hospitalized cohort but did not reduce viral load in outpatients. The nucleoside inhibitor molnupiravir prevented death but failed to prevent hospitalization. Nirmatrelvir, an inhibitor of the main protease (Mpro), co-dosed with the pharmacokinetic booster ritonavir, reduced hospitalization and death. Nirmatrelvir-ritonavir and molnupiravir received an Emergency Use Authorization in the United States at the end of 2021. Immunomodulatory drugs such as baricitinib, tocilizumab and corticosteroid, which target host-driven COVID-19 symptoms, are also in use. We highlight the development of COVID-19 therapies and the challenges that remain for anticoronavirals.
Insights
Antiviral therapies for coronavirus disease 2019 (COVID-19) are crucial for unvaccinated and immunocompromised individuals. Nirmatrelvir-ritonavir and molnupiravir show promise in reducing severe outcomes, though challenges remain for developing new antiviral drugs.
Area of Science:
- * Virology
- * Infectious Diseases
- * Pharmacology
Background:
- * Vaccines and monoclonal antibodies were developed rapidly for COVID-19 prevention.
- * A significant need persists for effective therapeutics in non-vaccinated, immunocompromised, or waning immunity populations.
- * Early investigational therapies demonstrated mixed efficacy, highlighting the need for robust treatment options.
Purpose of the Study:
- * To review the development of therapeutic agents for treating COVID-19.
- * To discuss the efficacy and limitations of various antiviral and immunomodulatory treatments.
- * To identify ongoing challenges in the development of novel anticoronavirals.
Main Methods:
- * Review of clinical trial data for investigational COVID-19 therapies.
- * Analysis of repurposed drugs, including nucleoside inhibitors and protease inhibitors.
- * Examination of immunomodulatory agents targeting host responses.
Main Results:
- * AT-527 showed viral load reduction in hospitalized patients but not outpatients.
- * Molnupiravir reduced mortality but did not prevent hospitalization.
- * Nirmatrelvir-ritonavir significantly reduced hospitalization and death, receiving Emergency Use Authorization.
- * Immunomodulatory drugs like baricitinib and tocilizumab are utilized for symptom management.
Conclusions:
- * Nirmatrelvir-ritonavir and molnupiravir represent key advancements in COVID-19 treatment.
- * Continued research is essential to overcome challenges in developing broadly effective and accessible antiviral therapies.
- * A combination of antiviral and immunomodulatory strategies may be necessary for comprehensive COVID-19 management.
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