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Multidisciplinary research efforts on potential COVID-19 vaccine and therapeutic candidates have increased since the pandemic outbreak of SARS-CoV-2 in 2019. This search has become imperative due to the increasing emergences and limited widely available medicines. The presence of bioactive anti-SARS-CoV-2 molecules was examined from various plant sources. Among them is a group of proteins called lectins that can bind carbohydrate moieties. In this article, we present ten novel, chitin-specific Hevein-like lectins that were derived from Selaginella moellendorffii v1.0's genome. The capacity of these lectin homologs to bind with the spike protein of SARS-CoV-2 was examined. Using the HDOCK server, 3D-modeled Hevein-domains were docked to the spike protein's receptor binding domain (RBD). The Smo446851, Smo125663, and Smo99732 interacted with Asn343-located complex N-glycan and RBD residues, respectively, with binding free energies of -17.5, -13.0, and -26.5 Kcal/mol. The molecular dynamics simulation using Desmond and the normal-state analyses via torsional coordinate association for the Smo99732-RBD complex using iMODS is characterized by overall higher stability and minimum deformity than the other lectin complexes. The three lectins interacting with carbohydrates were docked against five individual mutations that frequently occur in major SARS-CoV-2 variants. These were in the spike protein's receptor-binding motif (RBM), while Smo125663 and Smo99732 only interacted with the spike glycoprotein in a protein-protein manner. The precursors for the Hevein-like homologs underwent additional characterization, and their expressional profile in different tissues was studied. These in silico findings offered potential lectin candidates targeting key N-glycan sites crucial to the virus's virulence and infection.
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Introduction: The lack of feasible therapies and comorbidities aggravate the COVID-19 case-fatality rate (CFR). However, reports examining CFR associations with diabetes, concomitant cardiovascular diseases, chronic kidney disease, and chronic liver disease (CLD) are limited. More studies assessing hydroxychloroquine (Hcq) and antivirals are needed. Purpose: To examine associations of COVID-19 CFR in comorbid patient groups each with single comorbidities and after treatment with Hcq, favipiravir, and dexamethasone (Dex), either alone or in combination versus standard care. Methods: Using statistical analysis, we descriptively determined these associations among 750 COVID-19 patient groups during the last quarter of 2021. Results: A diabetes comorbidity (40%, n=299) showed twice the fatality (CFR 14%) of the others (CFR 7%; P=0.001). Hypertension (Htn) was the second-commonest comorbidity (29.5%, n=221), with similar CFR to diabetes (15% and 7% for Htn and non-Htn, respectively), but with higher significance (P=0.0006167). Although only 4% (n=30) heart failure (HF) was reported, the CFR (40%) was much higher than in those without it (8%). A similar rate (4%) for chronic kidney disease was reported, with CFRs of 33% and 9% among those with and without it, respectively (P=0.00048). Ischemic heart disease was 11% (n=74), followed by chronic liver disease (0.4%) and history of smoking (1%); however, these were not significant due to the sample sizes. Treatment indicated standard care and Hcq alone or in combination were superior (CFR of 4% and 0.5%, respectively) compared to favipiravir (25%) or Dex (38.5%) independently or in combination (35.4%). Furthermore, Hcq performed well (CFR 9%) when combined with Dex (9%; P=4.28-26). Conclusion: The dominance of diabetes and other comorbidities with significant association with CFR implied existence of a common virulence mechanism. The superiority of low-dose Hcq and standard care over antivirals warrants further studies.
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Coinfections and comorbidities add additional layers of difficulties into the challenges of COVID-19 patient management strategies. However, studies examining these clinical conditions are limited. We have independently investigated the significance of associations of specific bacterial species and different comorbidities in the outcome and case fatality rates among 129 hospitalized comorbid COVID-19 patients. For the first time, to best of our knowledge, we report on the predominance of Klebsiella pneumoniae and Acinetobacter baumannii in COVID-19 non-survival diabetic patients The two species were significantly associated to COVID-19 case fatality rates (p-value = 0.02186). Coinfection rates of Klebsiella pneumoniae and Acinetobacter baumannii in non-survivors were 93% and 73%, respectively. Based on standard definitions for antimicrobial resistance, Klebsiella pneumoniae and Acinetobacter baumannii were classified as multidrug resistant and extremely drug resistant, respectively. All patients died at ICU with similar clinical characterisitics. Of the 28 major coinfections, 24 (85.7%) were in non-survivor diabetic patients, implying aggravating and worsening the course of COVID-19. The rates of other comorbidities varied: asthma (47%), hypertension (79.4%), ischemic heart disease (71%), chronic kidney disease (35%), and chronic liver disease (32%); however, the rates were higher in K. pneumoniae and were all concomitantly associated to diabetes. Other bacterial species and comorbidities did not have significant correlation to the outcomes. These findings have highly significant clinical implications in the treatment strategies of COVID-19 patients. Future vertical genomic studies would reveal more insights into the molecular and immunological mechanisms of these frequent bacterial species. Future large cohort multicenter studies would reveal more insights into the mechanisms of infection in COVID-19.
