Simulation of gold nanoparticle movement through normal and cancer cell membranes.

Gold nanoparticles (Au-NPs) have been used for a long time to target cancer cells. Different modalities have been suggested to utilize Au-NPs in cancer patients. We construct both normal and cancer cell membranes to simulate the Au-NP entry to understand better how it can penetrate the cancer cell membrane. We use molecular dynamics simulation (MDS) on both normal and cancer cell membrane models for 150 ns. At the same time, we prepared the Au-NP of spherical shape (16 nm radius) capped with citrate using MDS for 100 ns. Finally, we added the Au-NP close to the membranes and moved it using 1000 kJ mol-1 nm-1 force constant during the 7.7 ns MDS run. We analyzed the membranes in the presence and absence of the Au-NP and compared normal and cancer membranes. The results show that normal cell membranes have higher stability than cancer membranes. Additionally, Au-NP forms pore in the membranes that facilitate water and ions entry during the movement inside the lipid bilayer region. These pores are responsible for the enhanced response of Au-NP-loaded chemotherapeutic agents in cancer treatment.

How helpful were molecular dynamics simulations in shaping our understanding of SARS-CoV-2 spike protein dynamics?

The SARS-CoV-2 spike protein (S) represents an important viral component that is required for successful viral infection in humans owing to its essential role in recognition of and entry to host cells. The spike is also an appealing target for drug designers who develop vaccines and antivirals. This article is important as it summarizes how molecular simulations successfully shaped our understanding of spike conformational behavior and its role in viral infection. MD simulations found that the higher affinity of SARS-CoV-2-S to ACE2 is linked to its unique residues that add extra electrostatic and van der Waal interactions in comparison to the SARS-CoV S. This illustrates the spread potential of the pandemic SARS-CoV-2 relative to the epidemic SARS-CoV. Different mutations at the S-ACE2 interface, which is believed to increase the transmission of the new variants, affected the behavior and binding interactions in different simulations. The contributions of glycans to the opening of S were revealed via simulations. The immune evasion of S was linked to the spatial distribution of glycans. This help the virus to escape the immune system recognition. This article is important as it summarizes how molecular simulations successfully shaped our understanding of spike conformational behavior and its role in viral infection. This will pave the way to us preparing for the next pandemic as the computational tools are tailored to help fight new challenges.

The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?

INTRODUCTION: Drugs that have demonstrated good activity against any member of the Orthopoxvirus genus are good candidates for repurposing studies against the mpox virus (MPXV). The conserved biology of poxviruses has proven beneficial from a clinical virology perspective. Evolutionarily conserved proteins tend to function in a highly similar way. Indeed, the smallpox vaccine was found to be 85% effective in protecting humans from mpox virus infection. Similarly, tecovirimat, the drug of choice for smallpox infections, was recently repurposed as a treatment option for mpox cases in Europe. AREA COVERED: This review article focuses on drug repurposing strategies to combat the newly emerged MPXV outbreak. The viral and host cell protein targets are challenged with a bunch of drugs and drug-like molecules in silico, in vitro, and in vivo. Some drugs show promising results and can be repurposed to eradicate MPXV infection. The authors also highlight potential limitations and provide their expert perspectives. EXPERT OPINION: Overall, it is clear that we cannot solely rely on the conventional drug discovery pipeline to find new treatments, despite advances in computational and experimental advances in the last few decades. Drug repurposing has successfully identified good candidate drugs against MPXV as it is one of the Orthopoxvirus genus family. Tecovirimat, brincidofovir, and cidofovir have shown promising results in preventing virus propagation. Consequently, drug repurposing represents an important strategy for the fast identification of new therapeutic options.