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Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

ABSTRACT: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to more than 20 million people infected worldwide with an average mortality rate of 3.6%. This virus poses major challenges to public health, as it not only is highly contagious but also can be transmitted by asymptomatic infected individuals. COVID-19 is clinically difficult to manage due to a lack of specific antiviral drugs or vaccines. In this article, Chinese therapy strategies for treating COVID-19 patients, including current applications of traditional Chinese medicine (TCM), are comprehensively reviewed. Furthermore, 72 small molecules from natural products and TCM with reported antiviral activity against human coronaviruses (CoVs) are identified from published literature, and their potential applications in combating SARS-CoV-2 are discussed. Among these, the clinical efficacies of some accessible drugs such as remdesivir (RDV) and favipiravir (FPV) for COVID-19 are emphatically summarized. We hope this review provides a foundation for managing the worsening pandemic and developing antivirals against SARS-CoV-2.

SUBMITTER: Choudhry N

PROVIDER: S-EPMC7489051 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.

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Chinese Therapeutic Strategy for Fighting COVID-19 and Potential Small-Molecule Inhibitors against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

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