Abstract
The outbreak of the COVID-19 pandemic in China has become an urgent health and economic challenge. The objective of the current work was to evaluate the efficacy of the combined complex of Sitagliptin (SIT) with melittin (MEL) against SARS-CoV-2 virus. SIT-MEL nano-conjugates were optimized by a full three-factor bi-level (23) factorial design. In addition, SIT concentration (mM, X1), MEL concentration (mM, X2), and pH (X3) were selected as the critical factors. Particle size (nm, Y1) and zeta potential (mV, Y2) were assessed as responses. Characterization of the optimized formula for Fourier-transformed infrared (FTIR) was carried out. The optimized formula showed particle size and zeta potential values of 77.42 nm and 27.67 mV, respectively. When compared with SIT and MEL, the combination of SIT-MEL complex has shown anti-viral potential against isolate of SARS-CoV-2 with IC50 values of 8.439 μM with significant improvement (p < 0.001). In addition, the complex showed IC50 in vitro 3CL-protease inhibition with IC50 7.216 µM. Molecular docking has revealed that formula components have good predicted pocket accommodation of the SARS-CoV-2 3-CL protease. An optimized formulation of SIT-MEL could guarantee both enhanced delivery to the target cells and the enhanced cellular uptake with promising activities against SARS-CoV-2.
Highlights
Owing to its epidemic levels, the recent outbreak of COVID-19 in China has emerged as an urgent health and economic challenge [1,2]
Identifying the formulation and process factors that could contribute to the drug delivery system attributes is pivotal in the field of developing pharmaceutical formulations
Analysis of Variance (ANOVA) was used to examine the significance of the studied variables
Summary
Owing to its epidemic levels, the recent outbreak of COVID-19 in China has emerged as an urgent health and economic challenge [1,2]. The new serious acute respiratory syndrome coronavirus 2 triggers COVID-19 (SARS-CoV-2) [3]. A meta-analysis suggested that the most common cardiometabolic comorbidities in COVID-19 hospitalized patients were hypertension, cardiovascular (CV) disease, and diabetes [7]. Arterial hypertension was confirmed by the first large cohort of hospitalized COVID-19 patients in Europe, followed by chronic heart disease and diabetes as the major comorbidities upon hospitalization [8,9], whereas the most common comorbidities were hypertension, obesity and diabetes in the intensive care unit (ICU) [10,11,12]. Recent studies indicate that even in younger patients, obesity can be associated with increased COVID-19 severity [13,14]. SIT may enhance glycol-metabolic regulation, which might gain from the clinical progression antagonism of COVID-19 [17]
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