Search Results (4)

Increasing evidence suggests bats are the ancestral hosts of the majority of coronaviruses. In general, coronaviruses primarily target the gastrointestinal system, while some strains, especially Betacoronaviruses with the most relevant representatives SARS-CoV, MERS-CoV, and SARS-CoV-2, also cause severe respiratory disease in humans and other mammals. We previously reported the susceptibility of Rousettus aegyptiacus (Egyptian fruit bats) to intranasal SARS-CoV-2 infection. Here, we compared their permissiveness to an oral infection versus respiratory challenge (intranasal or orotracheal) by assessing virus shedding, host immune responses, tissue-specific pathology, and physiological parameters. While respiratory challenge with a moderate infection dose of 1 × 10⁴ TCID₅₀ caused a systemic infection with oral and nasal shedding of replication-competent virus, the oral challenge only induced nasal shedding of low levels of viral RNA. Even after a challenge with a higher infection dose of 1 × 10⁶ TCID₅₀, no replication-competent virus was detectable in any of the samples of the orally challenged bats. We postulate that SARS-CoV-2 is inactivated by HCl and digested by pepsin in the stomach of R. aegyptiacus, thereby decreasing the efficiency of an oral infection. Therefore, fecal shedding of RNA seems to depend on systemic dissemination upon respiratory infection. These findings may influence our general understanding of the pathophysiology of coronavirus infections in bats. Full article

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first detected in Egypt in February 2020. Data about the prevalence rates of the SARS-CoV-2 lineages are relatively scarce. To understand the genetic characteristics of SARS-CoV-2 in Egypt during several waves of the pandemic, we analyzed sequences of 1256 Egyptian SARS-CoV-2 full genomes from March 2020 to May 2021. From one wave to the next, dominant strains have been observed to be replaced by other dominant strains. We detected an emerging lineage of SARS-CoV-2 in Egypt that shares mutations with the variant of concern (VOC). The neutralizing capacity of sera collected from cases infected with C.36.3 against dominant strains detected in Egypt showed a higher cross reactivity of sera with C.36.3 compared to other strains. Using in silico tools, mutations in the spike of SARS-CoV-2 induced a difference in binding affinity to the viral receptor. The C.36 lineage is the most dominant SARS-CoV-2 lineage in Egypt, and the heterotrophic antigenicity of SARS-CoV-2 variants is asymmetric. These results highlight the value of genetic and antigenic analyses of circulating strains in regions where published sequences are limited. Full article

Since the emergence of the pandemic of the coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the discovery of antiviral phytoconstituents from medicinal plants against SARS-CoV-2 has been comprehensively researched. In this study, thirty-three plants belonging to seventeen different families used traditionally in Saudi Arabia were tested in vitro for their ability to inhibit the SARS-CoV-2 main protease (M^PRO). Major constituents of the bio-active extracts were isolated and tested for their inhibition potential against this enzyme; in addition, their antiviral activity against the SARS-CoV-2 Egyptian strain was assessed. Further, the thermodynamic stability of the best active compounds was studied through focused comparative insights for the active metabolites regarding ligand–target binding characteristics at the molecular level. Additionally, the obtained computational findings provided useful directions for future drug optimization and development. The results revealed that Psiadia punctulata, Aframomum melegueta, and Nigella sativa extracts showed a high percentage of inhibition of 66.4, 58.7, and 31.5%, against SARS-CoV-2 M^PRO, respectively. The major isolated constituents of these plants were identified as gardenins A and B (from P. punctulata), 6-gingerol and 6-paradol (from A. melegueta), and thymoquinone (from N. sativa). These compounds are the first to be tested invitro against SARS-CoV-2 M^PRO. Among the isolated compounds, only thymoquinone (THY), gardenin A (GDA), 6-gingerol (GNG), and 6-paradol (PAD) inhibited the SARS-CoV-2 M^PRO enzyme with inhibition percentages of 63.21, 73.80, 65.2, and 71.8%, respectively. In vitro assessment of SARS-CoV-2 (hCoV-19/Egypt/NRC-03/2020 (accession number on GSAID: EPI_ISL_430820) revealed a strong-to-low antiviral activity of the isolated compounds. THY showed relatively high cytotoxicity and was anti-SARS-CoV-2, while PAD demonstrated a cytotoxic effect on the tested VERO cells with a selectivity index of CC₅₀/IC₅₀ = 1.33 and CC₅₀/IC₅₀ = 0.6, respectively. Moreover, GNG had moderate activity at non-cytotoxic concentrations in vitro with a selectivity index of CC₅₀/IC₅₀ = 101.3/43.45 = 2.3. Meanwhile, GDA showed weak activity with a selectivity index of CC₅₀/IC₅₀ = 246.5/83.77 = 2.9. The thermodynamic stability of top-active compounds revealed preferential stability and SARS-CoV-2 M^PRO binding affinity for PAD through molecular-docking-coupled molecular dynamics simulation. The obtained results suggest the treating potential of these plants and/or their active metabolites for COVID-19. However, further in-vivo and clinical investigations are required to establish the potential preventive and treatment effectiveness of these plants and/or their bio-active compounds in COVID-19. Full article

The emergence of the SARS-CoV-2 pandemic has prompted scientists to search for an efficient antiviral medicine to overcome the rapid spread and the marked increase in the number of patients worldwide. In this regard natural products could be a potential source of substances active against coronavirus infections. A systematic computer-aided virtual screening approach was carried out using commercially available natural products found on the Zinc Database in addition to an in-house compound library to identify potential natural product inhibitors of SARS-CoV-2 main protease (M^PRO). The top eighteen hits from the screening were selected for in vitro evaluation on the viral protease (SARS-CoV-2 M^PRO). Five compounds (naringenin, 2,3′,4,5′,6-pentahydroxybenzophenone, apigenin-7-O-glucoside, sennoside B, and acetoside) displayed high activity against the viral protein. Acteoside showed similar activity to the positive control GC376. The most potent compounds were tested in vitro on SARS-CoV-2 Egyptian strain where only naringenin showed moderate anti-SARS-CoV-2 activity at non-cytotoxic micromolar concentrations in vitro with a significant selectivity index (CC₅₀/IC₅₀ = 178.748/28.347 = 6.3). Moreover; a common feature pharmacophore model was generated to explain the requirements for enzyme inhibition by this diverse group of active ligands. These results pave a path for future repurposing and development of natural products to aid in the battle against COVID-19. Full article