Miniaturized click chemistry and direct screening facilitate the discovery of triazole piperazine SARS-CoV-2 M inhibitors with improved metabolic stability.

The continuous mutational nature of SARS-CoV-2 and its inter-species' similarities emphasize the urgent need to design and develop more direct-acting antiviral agents against highly infectious variants. Herein, we report on the efficient discovery of potent non-covalent non-peptide-derived M inhibitors using miniaturized click chemistry and direct screening. Based on the privileged piperazine scaffold, 68 triazole-containing derivatives were assembled and screened.

Longitudinal Monitoring of the Effects of Anti-Adenoviral Treatment Regimens in a Permissive In Vivo Model.

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement.

NPP-669, a prodrug of cidofovir, is highly efficacious against human adenovirus infection in the permissive Syrian hamster model.

Human adenoviruses can cause serious, disseminated infections in immunocompromised patients. For pediatric allogeneic stem cell transplant patients, the case fatality rate can reach 80%. Still, there is no available antiviral drug that is specifically approved by the Food and Drug Administration for the treatment of adenovirus infections.

Oral USC-093, a novel homoserinamide analogue of the tyrosinamide (S)-HPMPA prodrug USC-087 has decreased nephrotoxicity while maintaining antiviral efficacy against human adenovirus infection of Syrian hamsters.

Adenovirus infections of immunocompromised humans are a significant source of morbidity and mortality. Presently, there is no drug specifically approved for the treatment of adenovirus infections by the FDA. The state-of-the-art treatment of such infections is the off-label use of cidofovir, an acyclic nucleotide phosphonate.