With over 50 million currently confirmed cases worldwide, including more than 1.3 million deaths, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, limited prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, 400 compounds from the antimicrobial "pandemic response box" library were screened for inhibiting properties against SARS-CoV-2. An initial screen on Vero E6 cells identified five compounds that inhibited SARS-CoV-2 replication. However, validation of the selected hits in a human lung cell line highlighted that only a single compound, namely Retro-2.1, efficiently inhibited SARS-CoV-2 replication. Additional analysis revealed that the antiviral activity of Retro-2.1 occurs at a post-entry stage of the viral replication cycle. Combined, these data demonstrate that stringent in vitro screening of preselected compounds in multiple cell lines refines the rapid identification of new potential antiviral candidate drugs targeting SARS-CoV-2.
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http://dx.doi.org/10.3390/microorganisms8121872 | DOI Listing |
Viruses
December 2024
Scientific Research Institute for Biological Safety Problems, Ministry of Health of Kazakhstan, Almaty 080409, Kazakhstan.
The global burden of COVID-19 continues to rise, and despite significant progress in vaccine development, there remains a critical need for effective treatments for the severe inflammation and acute lung injury associated with SARS-CoV-2 infection. In this study, we explored the antiviral properties of a plant-derived complex consisting of flavonol and hydroxyorganic acid compounds. Our research focused on the ability of the flavonol and hydroxyorganic acid complex to suppress the activity of several key proteins involved in the replication and maturation of SARS-CoV-2.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
p97 (also known as valosin-containing protein, VCP) is a member of the AAA+ ATPase family and is intimately associated with protein quality control and homeostasis regulation. Therefore, pharmaceutical inhibition of p97 has been actively pursued as an anticancer strategy. Recently, p97 has emerged as an important pro-viral host factor and p97 inhibitors are being evaluated as potential antiviral agents.
View Article and Find Full Text PDFPathogens
December 2024
Unidad de Investigación Biomédica de Zacatecas, Instituto Mexicano del Seguro Social, Zacatecas 98000, Mexico.
The development of antivirals for respiratory viruses has advanced markedly in response to the growing threat of pathogens such as Influenzavirus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2. This article reviews the advances and challenges in this field, highlighting therapeutic strategies that target critical stages of the viral replication cycle, including inhibitors of viral entry, replication, and assembly. In addition, innovative approaches such as inhibiting host cellular proteins to reduce viral resistance and repurposing existing drugs are explored, using advanced bioinformatics tools that optimize the identification of antiviral candidates.
View Article and Find Full Text PDFMolecules
January 2025
Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China.
Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics to deal with the variants of SARS-CoV-2. (MH) is a herbal medicine credited with antiviral effects. This study aims to investigate the antiviral effects and the underlying mechanism of aqueous extract of (AEMH) for treating SARS-CoV-2.
View Article and Find Full Text PDFLife (Basel)
January 2025
Department of Clinical Medicine and Surgery, University of Naples "Federico II", 80131 Naples, Italy.
The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly impacted global health, with pneumonia emerging as a major complication in severe cases. The pathogenesis of COVID-19 is marked by the overproduction of reactive oxygen species (ROS) and an excessive inflammatory response, resulting in oxidative stress and significant tissue damage, particularly in the respiratory system. Antioxidants have garnered considerable attention for their potential role in managing COVID-19 pneumonia by mitigating oxidative stress and modulating immune responses.
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