Background: Tuberculosis is one of the most frequent and persistent global diseases causing millions of deaths every year. Pakistan lies at number 6 among the 22 most dominant countries, with multidrug resistance up to 15%. Isoniazid-resistant strains of Mycobacterium tuberculosis are gradually rising and seem to be more prevalent in developing countries. Mutations in the katG gene are considered to be responsible for the accusation of isoniazid resistance in M. tuberculosis. Objectives: The current study was designed to investigate the structural and functional associations of KatG gene mutations (S315R and S315T) and multidrug resistance in M. tuberculosis isolates from Karachi, Pakistan. Results: The present study revealed conformational changes in the structure of the KatG enzyme due to observed mutations, which led to induced alterations in isoniazid binding residues at the active site of the KatG enzyme. Furthermore, substantial changes were observed in interaction energy, ligand-receptor energy, electrostatic energy, salvation energy, and ligand-receptor conformational entropy. All these resultant modifications due to S315R and S315T mutations ultimately reduced the flexibility and stability of proteins at isoniazid-binding residues. Conclusions: This deviation in the consistency of protein texture eventually compromises the enzyme activity. It is well expected that the outcomes of the current study would provide a better understanding of the consequences of these mutations and provide a detailed insight into some previously unknown features.
The novel coronavirus pandemic of 2019 (COVID-19) has significantly harmed numerous social and economic activities worldwide, drawing researchers and governments’ attention to the problem and tackling it via persistent healthcare measures. The study’s primary purpose is to examine the effects of total coronavirus cases, total fatalities, total recovered cases, unemployment, and trade openness on stock prices and economic growth in the world’s top 39 affected nations. An analysis of the coronavirus outbreaks found that wealthier countries had a well-established healthcare infrastructure, but they were disproportionately affected by the virus. Conversely, the less wealthy nations had inadequate healthcare infrastructures, but they were not as affected as the wealthier countries. Is it possible to buy health with money? That was the question at the heart of the study’s money-and-health curve. The robust least square regression results indicate that an increase in coronavirus cases influences economic growth and stock market performance due to massive healthcare funding distributed globally, sustaining economic and financial activities for a shorter period. However, a continuous increase in coronavirus fatalities depresses the stock market, resulting in financial depression worldwide. Additionally, a rise in overall coronavirus recovered cases has a negative effect on the country’s economic development and stock market performance because of greater uncertainty in economic and financial activities. Case fatality ratios influence economic growth, whereas case recovery ratios decrease economic and financial performance due to greater healthcare concerns across countries. Finally, trade openness is critical in sustaining the country’s economic development and stock market performance in the wake of the COVID-19 epidemic.
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