Abstract
The newly emerged severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) coronavirus initiated a pneumonia outbreak (COVID-19) that rapidly spread worldwide and quickly became a public health emergency of international concern; However to date, except Remdesivir, there are no clinically approved specific or effective medicines to prevent or treat COVID-19. Therefore, the development of novel treatments against coronavirus infections caused by the current SARS-CoV-2 virus, as well as other highly pathogenic human coronaviruses, represents an urgent unmet need. Stimulator of interferon genes (STING) plays a central role in host defense mechanisms against microbial infections. STING activation leads to the induction of both type I interferon and autophagy responses, which elicit strong inhibitory effect against the infections caused by a broad range of microbial pathogens. However, whether STING activation can impact infections from SARS-CoV-2 or other coronaviruses remains largely unknown. In this study, we investigated the anti-coronavirus activity triggered by STING activation. We discovered that dimeric amidobenzimidazole (diABZI), a synthetic small molecule STING receptor agonist, showed potent anti-coronavirus activity against both the common cold human coronavirus 229E (HCoV-229E) and SARS-CoV-2 in cell culture systems. In addition, we demonstrated that the antiviral activity of diABZI was dependent on the interferon pathway in HCoV-229E infected normal human fibroblast lung cells (MRC-5) and reconstituted primary human airway air-liquid interface (ALI) cultures. Furthermore, low-dose of diABZI treatment at 0.1 μM effectively reduced the SARS-CoV-2 viral load at the epithelial apical surface and prevented epithelial damage in the reconstituted primary human bronchial airway epithelial ALI system. Our findings have thus revealed the therapeutic potential of STING agonists, such as diABZI, as treatments for SARS-CoV-2 and other human coronavirus infections.
Keywords: Coronavirus; HCoV-229E; SARS-CoV-2; STING agonist; diABZI.
【저자키워드】 SARS-CoV-2, coronavirus, HCoV-229E, STING agonist, diABZI., 【초록키워드】 COVID-19, Treatment, Coronavirus infection, Pneumonia, Infection, interferon, Remdesivir, SARS-CoV-2 virus, antiviral activity, autophagy, type I interferon, airway, Human coronavirus, Spread, Medicine, Coronavirus infections, Viral load, outbreak, low-dose, International, HCoV, pathway, HCoV-229E, Pathogens, small molecule, receptor, public health emergency, common cold, epithelial, mechanism, STING, human coronaviruses, 229E, Air-liquid interface, host defense, interferon pathway, defense mechanisms, microbial, unmet need, Activation, other coronaviruses, SARS-CoV-2 viral load, therapeutic potential, inhibitory effect, treat, cultures, Defense, human coronavirus 229E, microbial infections, highly pathogenic, primary human airway, apical surface, fibroblast, Host, stimulator, responses, Prevent, effective, anti-coronavirus activity, lung cell, cell culture systems, agonists, caused, addition, investigated, clinically, approved, reduced, other coronavirus, dependent on, demonstrated, elicit, initiated, triggered, the interferon, prevented, dimeric, the SARS-CoV-2, 【제목키워드】 Coronavirus infection, inhibition, primary human airway,