Structure and Dynamics of Zika Virus Protease and Its Insights into Inhibitor Design

Zika virus (ZIKV)—a member of the Flaviviridae family—is an important human pathogen. Its genome encodes a polyprotein that can be further processed into structural and non-structural proteins. ZIKV protease is an important target for antiviral development due to its role in cleaving the polyprotein to release functional viral proteins. The viral protease is a two-component protein complex formed by NS2B and NS3. Structural studies using different approaches demonstrate that conformational changes exist in the protease. The structures and dynamics of this protease in the absence and presence of inhibitors were explored to provide insights into the inhibitor design. The dynamic nature of residues binding to the enzyme cleavage site might be important for the function of the protease. Due to the charges at the protease cleavage site, it is challenging to develop small-molecule compounds acting as substrate competitors. Developing small-molecule compounds to inhibit protease activity through an allosteric mechanism is a feasible strategy because conformational changes are observed in the protease. Herein, structures and dynamics of ZIKV protease are summarized. The conformational changes of ZIKV protease and other proteases in the same family are discussed. The progress in developing allosteric inhibitors is also described. Understanding the structures and dynamics of the proteases are important for designing potent inhibitors.

Research progress of new coronavirus (COVID-19): Theoretical study: تقدم البحوث المتعلقة بفيروس كورونا الجديد (كوفيد-19): دراسة نظرية

Objective: Provide a holistic perspective the new coronavirus (covid-19) to assist researchers and improving areas for future response plans to deal with these diseases, and to provide a summary of the factors that help stop their development. Methods: This is a theoretical study conducted through a comprehensive review of the literature and research in the research engines (PubMed), (Read) and (ELSEVIER) and other new studies published in Chinese. Results: Until now no effective drug for the treatment of new coronavirus pneumonia (covid-19) has been found. The development of vaccines is still in animal experiments. Recommendations and measures to control the spread of infection are still the only way to prevent the spread of covid-19 virus. However, some drugs have been proven effective. Effectively alleviates virus-associated infections (Covid-19) and also used certain factors during the SARS and MERS epidemics. For example, lopinavir (LPV) is an effective drug to inhibit protease activity of coronavirus. Significant progress has been made in diagnosis, as some studies have found that CT scans may show certain abnormalities in the chest even before symptoms appear. Discussion: The COVID-19 virus remains a global concern and more research is needed to control it. It needs to find all sources of infection, especially those that are still mysterious and still need to develop precautions, especially for hospitals staff and those who need direct contact with patients.