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Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

ABSTRACT: Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC₅₀ between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15-83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1-9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2-25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.

SUBMITTER: Zhang JL

PROVIDER: S-EPMC8646019 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), known to cause the disease COVID-19, was declared a pandemic in early 2020. The objective of this review was to collate information regarding the potential of plants and natural products to inhibit coronavirus and targets associated with infection in humans and to highlight known drugs, which may have potential activity against SARS-CoV-2. Due to the similarity in the RNA genome, main proteases, and primary host receptor between SARS-CoV and SARS-CoV-2, a review was conducted on plants and secondary metabolites, which have shown activity against SARS-CoV. Numerous scientific reports on the potential of plants and secondary metabolites against SARS-CoV infection were found, providing important information on their possible activity against SARS-CoV-2. Based on current literature, 83 compounds have been identified with the potential to inhibit COVID-19. The most prominent selectivity was found for the alkaloid, lycorine, the lignan, savinin, and the abietane terpenoid, 8-beta-hydroxyabieta-9(11),13-dien-12-one with selectivity index values greater than 945, 667, and 510, respectively. Plants and their secondary metabolites, with activity against targets associated with the SARS-CoV infection, could provide valuable leads for the development into drugs for the novel SARS-CoV-2. The prospects of using computational methods to screen secondary metabolites against SARS-CoV targets are briefly discussed, and the drawbacks have been highlighted. Finally, we discuss plants traditionally used in Southern Africa for symptoms associated with respiratory viral infections and influenza, such as coughs, fever, and colds. However, only a few of these plants have been screened against SARS-CoV. Natural products hold a prominent role in discovering novel therapeutics to mitigate the current COVID-19 pandemic; however, further investigations regarding in vitro, in vivo, pre-clinical, and clinical phases are still required.

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Azvudine is a thymus-homing anti-SARS-CoV-2 drug effective in treating COVID-19 patients.

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