Structural and virologic mechanism of the emergence of resistance to M inhibitors in SARS-CoV-2.

We generated SARS-CoV-2 variants resistant to three SARS-CoV-2 main protease (M) inhibitors (nirmatrelvir, TKB245, and 5h), by propagating the ancestral SARS-CoV-2 in VeroE6 cells with increasing concentrations of each inhibitor and examined their structural and virologic profiles. A predominant E166V-carrying variant (SARS-CoV-2), which emerged when passaged with nirmatrelvir and TKB245, proved to be resistant to the two inhibitors. A recombinant SARS-CoV-2 was resistant to nirmatrelvir and TKB245, but sensitive to 5h.

Does the loot box open the door to addiction? A case report of gaming disorder with high charges for loot box purchases.

Background: A loot box is a gaming term for an electronic lottery that randomly provides items that enhance the gaming experience. In recent years, loot boxes have been increasingly discussed as a risk factor of gaming disorder (GD). While they may be purchased for a few dollars at a time, the cumulative expenses resulting from their addictive use have become a social problem.

From Glycolysis to Viral Defense: The Multifaceted Impact of Glycolytic Enzymes on Human Immunodeficiency Virus Type 1 Replication.

Viruses require host cells to replicate and proliferate, which indicates that viruses hijack the cellular machinery. Human immunodeficiency virus type 1 (HIV-1) primarily infects CD4-positive T cells, and efficiently uses cellular proteins to replicate. Cells already have proteins that inhibit the replication of the foreign HIV-1, but their function is suppressed by viral proteins.

Total Syntheses of Phorbol and 11 Tigliane Diterpenoids and Their Evaluation as HIV Latency-Reversing Agents.

Tigliane diterpenoids possess exceptionally complex structures comprising common 5/7/6/3-membered ABCD-rings and disparate oxygen functionalities. While tiglianes display a wide range of biological activities, compounds with HIV latency-reversing activity can eliminate viral reservoirs, thereby serving as promising leads for new anti-HIV agents. Herein, we report collective total syntheses of phorbol () and 11 tiglianes - with various acylation patterns and oxidation states, and their evaluation as HIV latency-reversing agents.

HIV-1 Gag MA domain binds to cardiolipin in a binding mode distinct from virus assemble mediator PI(4,5)P.

The human immunodeficiency virus type 1 (HIV-1) Gag protein is responsible for facilitating HIV-1 virion assembly and budding. Our study demonstrates that cardiolipin (CL), a component found in the inner mitochondrial membrane, exhibits the highest binding affinity to the N-terminal MA domain of the HIV-1 Gag protein within the lipid group of host cells. To assess this binding interaction, we synthesized short acyl chain derivatives of CL and employed surface plasmon resonance (SPR) analysis to determine the dissociation constants (Kd) for CL and the MA domain.