ABSTRACT
Paxlovid™ is a combination of Nirmatrelvir and Ritonavir antiviral pills with good oral bioavailability. In clinical studies, treatment of the patients infected with SARS-CoV-2 with Paxlovid™ within three to five days of the appearance of symptoms significantly reduced the hospitalization rate as well as mortality. It is the first oral antiviral treatment for the COVID-19 which received USFDA approval for EUA on 22nd December, 2021. Nirmatrelvir inhibits the replication of SARS-CoV-2 while another antiviral drug, Ritonavir, is given in combination to enhance the bioavailability of Nirmatrelvir. Molecular interaction studies have shown that Nirmatrelvir binds covalently with the catalytic triad of the active site of the viral protease enzyme (3CLPRO). It, therefore, acts by stopping the SARS-CoV-2 replication by its ability to block the translation of the viral genetic materials. Research studies conducted have proven the efficacy of this oral anti-viral drug in mild to moderate COVID-19 patients beside its ease of oral administration and good oral bioavailability. Alternative synthetic methods to scale up the synthesis of this potent molecule are needed to reduce the treatment cost of the COVID-19. Extensive clinical research on a larger group population is also underway for ensuring the safety and efficacy of this medication in the battle against the COVID-19 pandemic.
ABSTRACT
Background and Objective: An enzyme that inhibits the receptor could make it more difficult for coronavirus to reach cells. The key protease necessary for coronavirus proteolytic maturation is the recognized coronavirus 3-chymotrypsin-like protease 3CLpro, also known as Mpro. This Mpro is needed for immune control and the cleavage of the polyproteins pp1a and pp1ab, making it a promising target for anti-COVID-19 drugs. As a result, inhibiting the Mpro enzyme inhibits viral maturation. Bioactive constituents obtained from some selected indigenous plants of India, which have been reported to have antiviral potential, were subjected to virtual screening against ACE-2 and Mpro in the current study. Materials and Methods: Cresset's Flare 4.0 was used to establish the 3-D structure of all the compounds. Complete optimizations of these constructed structures were carried out. While performing the minimization, the spin state of the wave function was set to the singlet and standard SCF convergence was used for optimization, all other parameters were left at their default values. The Protein Data Bank (https://www.rcsb.org) was used to download the 3-D structures of Mpro from COVID-19 (PDB ID 6LU7) and ACE-2 receptor from Human (PDB ID 1R4L). Results: The findings show that these phytochemicals can bind to ACE-2 and Mpro more effectively as compared to reference compounds and act as inhibitors. Conclusion: The findings of virtual screening of these bioactive constituents revealed that most of them are more active than the reference compounds. Therefore, they could be used to produce antiviral drugs against Coronavirus in the future.
ABSTRACT
Background: Anxiety is seen among students even during normal times. The COVID-19pandemic is believed to have increased anxiety and depression among the students. Purpose: An investigation was done to assess the anxiety levels and coping strategies of nursing students in Saudi Arabia. The influence of demographics on the anxiety levels and coping strategies were also determined. Methods: A cross-sectional study was conducted using a questionnaire through Google forms. The questionnaire had items related to demographics such as age, sex, etc., along with a question to know about the confidence of students to work as nurses. A GAD-7 scale was used to assess anxiety levels and BriefCope was used to determine coping strategies. Statistics were performed using non-parametric tests, factorial analysis, and linear regression. Results: More than half of the participating students experienced moderate to severe anxiety. The anxiety levels were not influenced significantly by demographics except the young age. More than 50% of the students were reluctant to work as nurses and this affected the anxiety score significantly. Factorial analysis grouped variables into six factors. Linear regression showed a positive correlation of these factors with anxiety. Conclusion: Anxiety score revealed that Saudi nursing students had moderate to severe anxiety. The combined number of students reluctant or scared to work was more than those who were confident to work as nurses. A positive association was observed between factor variables with mild and moderate anxiety.