As the spread of infections caused by hepatitis B virus (HBV) threatens public health worldwide, investigations from multiple perspectives and of various mechanisms of action are urgently required to increase the HBV cure rate. Targeting the encapsidation of the nuclear capsid protein (core protein, HBc) has emerged as an attractive strategy for inhibiting the viral assembly process; however, a drug targeting this mechanism has not yet been approved. We synthesized novel sulfamoylbenzamides (SBAs) as capsid assembly modulators of HBV and found that the effects and safety profiles of compounds 3 and 8 have potential therapeutic applicability against HBV. The formation of tubular particles was time-dependent in the presence of 3, indicating a new mode of protein assembly by SBA compounds. Our findings provide a new entity for developing safe and efficient treatments for HBV infection.

Gemcitabine is a nucleoside analogue of deoxycytidine and has been reported to be a broad-spectrum antiviral agent against both DNA and RNA viruses. Screening of a nucleos(t)ide analogue-focused library identified gemcitabine and its derivatives (compounds 1, 2a, and 3a) blocking influenza virus infection. To improve their antiviral selectivity by reducing cytotoxicity, 14 additional derivatives were synthesized in which the pyridine rings of 2a and 3a were chemically modified. Structure-and-activity and structure-and-toxicity relationship studies demonstrated that compounds 2e and 2h were most potent against influenza A and B viruses but minimally cytotoxic. It is noteworthy that in contrast to cytotoxic gemcitabine, they inhibited viral infection with 90% effective concentrations of 14.5–34.3 and 11.4–15.9 μM, respectively, maintaining viability of mock-infected cells over 90% at 300 μM. Resulting antiviral selectivity was comparable to that of a clinically approved nucleoside analogue, favipiravir. The cell-based viral polymerase assay proved the mode-of-action of 2e and 2h targeting viral RNA replication and/or transcription. In a murine influenza A virus-infection model, intraperitoneal administration of 2h not only reduced viral RNA level in the lungs but also alleviated infection-mediated pulmonary infiltrates. In addition, it inhibited replication of severe acute respiratory syndrome virus 2 infection in human lung cells at subtoxic concentrations. The present study could provide a medicinal chemistry framework for the synthesis of a new class of viral polymerase inhibitors.

Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).