Do the Covid-19 vaccines affect the reproductive parameters of men?-A Northern Saudi experience.

Background: The COVID-19 vaccine acceptance is a psychological behavior influenced by many factors, including fear of an adverse effect on the reproductive system. Aims: The aim of this study is to assess the COVID-19 vaccines effect on reproductive parameters among the male population of northern Saudi Arabia. Patients and Methods: We conducted a prospective cohort study among 100 volunteers who received two doses of COVID-19 vaccines. A pre- and post-vaccination blood sample was collected and analyzed for testosterone, prolactin, and follicle-stimulating hormone (FSH). Semen samples were also collected and analyzed. The Wilcoxon signed-rank test was used to compare the values between pre- and post-vaccination. Results: Of the 100 samples analyzed, there was a significant increase in progressive sperm motility after the second dose of vaccination, but the increase was within the physiological limits (pre-55.03 [42.00-61.75] vs. post-57.50 [42.25-63.00], P = 0.008). Similarly, a significant increase in serum testosterone level after the second vaccination dose was observed (pre-380.65 [301.60-485.73] vs. post-410 [318.18-505.35], P = 0.016). Conclusion: These preliminary results show that the COVID-19 vaccines do not have any adverse effect on the reproductive parameters of men. A prospective long-term follow-up study will be necessary on all WHO -approved COVID vaccines to determine their long-term effect on men's reproductive health. The future follow-up study could strengthen our findings and encourage the men who have vaccine hesitancy to take due to fear of its effect on reproductive parameters.

Discovery of Zafirlukast as a novel SARS-CoV-2 helicase inhibitor using in silico modelling and a FRET-based assay.

The coronavirus helicase is an essential enzyme required for viral replication/transcription pathways. Structural studies revealed a sulphate moiety that interacts with key residues within the nucleotide-binding site of the helicase. Compounds with a sulphoxide or a sulphone moiety could interfere with these interactions and consequently inhibit the enzyme. The molecular operating environment (MOE) was used to dock 189 sulphoxide and sulphone-containing FDA-approved compounds to the nucleotide-binding site. Zafirlukast, a leukotriene receptor antagonist used to treat chronic asthma, achieved the lowest docking score at -8.75 kcals/mol. The inhibitory effect of the compounds on the SARS-CoV-2 helicase dsDNA unwinding activity was tested by a FRET-based assay. Zafirlukast was the only compound to inhibit the enzyme (IC50 = 16.3 µM). The treatment of Vero E6 cells with 25 µM zafirlukast prior to SARS-CoV-2 infection decreased the cytopathic effects of SARS-CoV-2 significantly. These results suggest that zafirlukast alleviates SARS-CoV-2 pathogenicity by inhibiting the viral helicase and impairing the viral replication/transcription pathway. Zafirlukast could be clinically developed as a new antiviral treatment for SARS-CoV-2 and other coronavirus diseases. This discovery is based on molecular modelling, in vitro inhibition of the SARS-CoV helicase activity and cell-based SARS-CoV-2 viral replication.