Assessment of Tocilizumab (Humanized Monoclonal Antibody) for Therapeutic Efficacy and Clinical Safety in Patients with Coronavirus Disease (COVID-19).

Background and objectives: COVID-19 patients exhibit a broad range of manifestations, presenting with a flu-like respiratory tract infection that can advance to a systemic and severe disease characterized by pneumonia, pulmonary edema, severe damage to the airways, and acute respiratory distress syndrome (ARDS, causing fatality in 70% of COVID-19 cases). A 'cytokine storm' profile is found in most severely influenced COVID-19 patients. The treatment protocol of the disease also includes tocilizumab, which is a humanized monoclonal antibody used to treat autoimmune and inflammatory conditions. This study was designed (1) to assess the role of tocilizumab in COVID-19 patients regarding therapeutic efficacy through evaluation of cytokine release syndrome (CRS) resolution and anticoagulant effect, analyzing clinical safety via monitoring of associated adverse effects profile; and (2) to compare the clinical safety and therapeutic efficacy of institutional treatment regimen (alone) versus tocilizumab added to an institutional treatment module in COVID-19 patients. Materials and Methods: In this study, the endpoints parametric assessment of severely diseased patients of COVID-19 was performed (total n = 172, control group (institutional protocol treatment provided), n = 101 and test group (tocilizumab provided), n = 71) at the Khyber Teaching Institution, MTI, Peshawar. The assessments were compared using non-parametric analyses at baseline and after a follow-up of 12-18 days until the patient discharged or expired. Results: Results of the study revealed an insignificant difference among the control vs. test group in resolving inflammatory parameters (C-reactive protein (CRP) 21.30 vs. 50.07; p = 0.470, ferritin 482.9 vs. 211.5; p = 0.612, lactate dehydrogenase (LDH) 29.12 vs.18.8; p = 0.0863, and D-dimer 464 vs.164.4; p = 0.131). However, a statistically significant difference was found between the control group and test group regarding coagulation parameters (international normalized ratio (INR) 0.12 vs. -0.07; p ≤ 0.001; activated partial thromboplastin time (aPTT) 0.42 vs. -1.16; p ≤ 0.001; prothrombin time (PT) 0.31 vs. -0.96; p ≤ 0.001; platelet count -12.34 vs. -1.47; p = 0.012) and clinical survival rate (89.10 vs. 90.14; p < 0.001). Furthermore, there was significantly higher infection rates and raised alanine aminotransferase (ALT) and alkaline phosphatase (ALP) associated with the tocilizumab group as compared to those receiving institutional treatment (bacterial infections: 0.99% vs. 15.49%; p ≤ 0.01, ALT: 3.96% vs. 28.16%; p ≤ 0.01, ALP: 1.98% vs. 22.53%; p ≤ 0.01). Conclusions: From this study, it was concluded that tocilizumab can be a better drug of choice in terms of efficacy, particularly in resolving coagulopathy in severe COVID-19 patients.

The Role of Cannabis sativa L. as a Source of Cannabinoids against Coronavirus 2 (SARS-CoV-2): An In Silico Study to Evaluate Their Activities and ADMET Properties.

Cannabis sativa L. is an annual herbaceous plant that belongs to the family Cannabinaceae. In this study, the potential use of forty-five cannabinoids, previously identified from Cannabis sativa to alleviate COVID-19 infection via prohibition of crucial SARS-CoV-2 proteins using molecular docking, was examined. In silico studies were performed on three vital enzymes that serve as principle therapeutic targets to prevent SARS-CoV-2 replication. These enzymes are the main protease SARS-CoV-2 MPro, papain-like protease SARS-CoV-2 PLpro and angiotensin-converting enzyme 2 (ACE2). Regarding SARS-CoV-2 MPro, cannabichromanon (32) showed the best fitting within its active centers, followed by cannabinolic acid (22) and cannabinol (21), displaying ∆G of -33.63, -23.24, and -21.60 kcal/mol, respectively. Concerning SARS-CoV-2 PLpro, cannabichromanon (32) followed by cannabinolic acid (22) and cannabicyclolic acid (41) revealed the best binding within its active pockets owing to multiple bond formation with ∆G values of -28.36, -22.81, and -19.89 kcal/mol. Furthermore, cannabichromanon (32), cannabinolic acid (22), and cannabinol (21) showed considerable fitting within the active sites of angiotensin-converting enzyme 2 (ACE2) evidenced by their significant ∆G values that were estimated as -41.77, -31.34, and -30.36 kcal/mol, respectively. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) evaluation was performed on the tested cannabinoids to further explore their pharmacokinetics, pharmacodynamics, and toxicity properties. The results indicated the considerable pharmacokinetic, pharmacodynamic, and toxicity properties of cannabinol (21), cannabinolic acid (22), cannabichromanon (32), and cannabicyclolic acid (41) that showed best fitting scores within the active sites of the tested enzymes. Multivariate data analysis revealed that cannabichromanon and cannabinolic acid showed a discriminant nature and hence can be incorporated in pharmaceutical dosage forms to alleviate COVID-19 infection.

A Battle against COVID-19: Vaccine Hesitancy and Awareness with a Comparative Study between Sinopharm and AstraZeneca.

BACKGROUND: Awareness about the COVID-19 vaccine's adverse effects is crucial for gaining public trust. As we still lack proof of vaccines' safety, this survey aimed to investigate Egyptians' general awareness of the Sinopharm and AstraZeneca vaccines against COVID-19 and provide considerable evidence on their side effects and complications. METHODS: A cross-sectional questionnaire-based study was conducted in Egypt between 20 September and 10 October in 2021, with multiple-choice questions (MCQs) covering all data on vaccine administration confusion, adverse effects or intensity, and complications. RESULTS: Among the 390 participants, 42.3% reported being hesitant before receiving one of the vaccines. About 40.3% of participants were previously infected before getting vaccinated while only 4.6% reported being infected after vaccination. The AstraZeneca vaccine demonstrated higher side effects and symptoms than the Sinopharm vaccine while the Sinopharm vaccine showed a significantly higher rate of COVID-19 infection after vaccination. CONCLUSIONS: People with higher educational levels and chronic respiratory diseases represent an excellent model for accepting COVID-19 vaccination. A booster shot is recommended for people vaccinated with the Sinopharm vaccine due to a significantly higher rate of COVID-19 infection after vaccination; however, the Sinopharm vaccine shows a more acceptable safety profile.

Phytoconstituents, In Vitro Anti-Infective Activity of Buddleja indica Lam., and In Silico Evaluation of its SARS-CoV-2 Inhibitory Potential.

Phytochemical investigation of Buddleja indica Lam. leaves methanol extract (BIT) resulted in the isolation of six known compounds for the first time from the plant, namely, p-hydroxybenzoic acid 1), caffeic acid 2), quercetin 3-O-ß-D glucoside-7-O-α-L-rhamnoside 3), kaempferol 3-O-ß-D glucoside-7-O-α-L-rhamnoside 4), quercetin 7-O-ß-D glucoside 5) and kaempferol 6). BIT extract showed potent antibacterial activity with MIC values ranging between 0.48 and 1.95 µg/ml with Bacillus subtilis was the most susceptible to the BIT effect. It showed a notable antimycobacterial and anti-Helicobacter pylori activity with MIC values of 100 and 80 µg/ml, respectively. Vesicular stomatitis virus (VSV) was more sensitive to the antiviral activity of BIT comparable to herpes simplex virus type 1 (HSV-1), showing 48.38 and 41.85% inhibition of the viral replication at a dose of 50 µg/ml for VSV and HSV-1, respectively. In silico molecular docking of the isolated compounds revealed that caffeic acid 2) showed the highest fitting within the active sites of DNA-gyrase, topoisomerase IV, and SARS-CoV-2 MPro. Quercetin 7-O-ß-D glucoside 5) revealed the best fitting in dihydrofolate reductase active site with ∆ G value equals -36.53 Kcal/mol. Kaempferol 6) exhibited the highest fitting towards ß-lactamase, SARS-CoV-2PLpro, and SARS-CoV-2 3CLpro active sites. Thus, B. indica Lam. can be considered as a future source of cheap, substantially safe, and credible antibacterial, antifungal, and antiviral candidate of natural origin that could effectively participate in solving the problem of COVID-19 pandemic. These findings provide a scientific consolidation for the ethnomedicinal uses of Buddleja indica Lam. as a topical antiseptic.