Gut Microbiota: Potential Therapeutic Target for Sickle Cell Disease Pain and Complications.

Aim: Sickle cell disease has witnessed a 41.4% surge from 2000 to 2021, significantly affecting morbidity and mortality rates, particularly in children from regions with elevated under-5 mortality rates. Gut microbiota dysbiosis is increasingly recognised in SCD, exacerbating complications, particularly chronic pain, marked by significant alterations of proinflammatory bacteria abundance. This review explores the therapeutic potential of Akkermansia muciniphila and Roseburia spp. in alleviating SCD-related complications, emphasising their roles in maintaining gut barrier integrity, reducing inflammation, and modulating immune responses. Method: A literature search up to November 2023 using PubMed, MEDLINE, and Google Scholar databases explored SCD pathophysiology, gut microbiota composition, Akkermansia muciniphila and Roseburia spp. abundance, pain and gut dysbiosis in SCD, and butyrate therapy. Result: A. muciniphila and Roseburia spp. supplementation shows promise in alleviating chronic pain by addressing gut dysbiosis, offering new avenues for sustainable SCD management. This approach holds the potential for reducing reliance on reactive treatments and improving overall quality of life. This research underscores the pivotal role of the gut microbiome in SCD, advocating for personalised treatment approaches. Conclusion: Further exploration and clinical trials are needed to harness the full potential of these gut bacteria for individuals affected by this challenging condition.

The Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) Can Combat Cytokine Storm and Other COVID-19 Related Pathologies: A Review.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is characterized by acute respiratory distress syndrome (ARDS) facilitated by cytokine storm and other risk factors that increase susceptibility and complications leading to death. Emerging as a major global public health challenge, the disease has claimed more than 6 million lives and caused catastrophic global economic disruptions. However, there are concerns about the safety as well as the efficacy of drugs and vaccines presently used to control the pandemic, therefore necessitating intense global search for safe natural products that can effectively and safely combat it. This work reviews studies on lingzhi or reishi medicinal mushroom, Ganoderma lucidum and its properties that may potentially combat SARS-CoV-2 infection and the co-morbidities. Available evidence suggests that medicinal properties of the Ganoderma mushroom can combat the complications of SARS-CoV-2 infection and the co-morbidities that can aggravate the severity of the disease. Preclinical and clinical evaluation to establish dose, efficacy, and potential toxicity and possible use in the management of COVID-19 is recommended.

Identifying immunodominant multi-epitopes from the envelope glycoprotein of the Lassa mammarenavirus as vaccine candidate for Lassa fever.

Purpose: Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC). Materials and Methods: The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector. Results: A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS. Conclusion: The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.

RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2'-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION.

Background: The 2'-O-methyltransferase is responsible for the capping of SARS-CoV-2 mRNA and consequently the evasion of the host's immune system. This study aims at identifying prospective natural inhibitors of the active site of SARS-CoV-2 2'O-methyltransferase (2'-OMT) through an in silico approach. Materials and methods: The target was docked against a library of natural compounds obtained from edible African plants using PyRx - virtual screening software. The antiviral agent, Dolutegravir which has a binding affinity score of -8.5 kcal mol-1 with the SARS-CoV-2 2'-OMT was used as a standard. Compounds were screened for bioavailability through the SWISSADME web server using their molecular descriptors. Screenings for pharmacokinetic properties and bioactivity were performed with PKCSM and Molinspiration web servers respectively. The PLIP and Fpocket webservers were used for the binding site analyses. The Galaxy webserver was used for simulating the time-resolved motions of the apo and holo forms of the target while the MDWeb web server was used for the analyses of the trajectory data. Results: The Root-Mean-Square-Deviation (RMSD) induced by Rhamnetin is 1.656A0 compared to Dolutegravir (1.579A0). The average B-factor induced by Rhamnetin is 113.75 while for Dolutegravir is 78.87; the Root-Mean-Square-Fluctuation (RMSF) for Rhamnetin is 0.75 and for Dolutegravir is 0.67. Also, at the active site, Rhamnetin also has a binding affinity score of -9.5 kcal mol-1 and forms 7 hydrogen bonds compared to Dolutegravir which has -8.5 kcal mol-1 and forms 4 hydrogen bonds respectively. Conclusion: Rhamnetin showed better inhibitory activity at the target's active site than Dolutegravir.

Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach.

BACKGROUND: Brucellosis is an infectious disease caused by bacteria of the genus Brucella. Although it is the most common zoonosis worldwide, there are increasing reports of drug resistance and cases of relapse after long term treatment with the existing drugs of choice. This study therefore aims at identifying possible natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silico approach. METHODS: Using PyRx 0.8 virtual screening software, the target was docked against a library of natural compounds obtained from edible African plants. The compound, 2-({3-[(3,5-dichlorobenzyl) amino] propyl} amino) quinolin-4(1H)-one (OOU) which is a co-crystallized ligand with the target was used as the reference compound. Screening of the molecular descriptors of the compounds for bioavailability, pharmacokinetic properties, and bioactivity was performed using the SWISSADME, pkCSM, and Molinspiration web servers respectively. The Fpocket and PLIP webservers were used to perform the analyses of the binding pockets and the protein ligand interactions. Analysis of the time-resolved trajectories of the Apo and Holo forms of the target was performed using the Galaxy and MDWeb servers. RESULTS: The lead compounds, Strophanthidin and Isopteropodin are present in Corchorus olitorius and Uncaria tomentosa (Cat's-claw) plants respectively. Isopteropodin had a binding affinity score of -8.9 kcal / ml with the target and had 17 anti-correlating residues in Pocket 1 after molecular dynamics simulation. The complex formed by Isopteropodin and the target had a total RMSD of 4.408 and a total RMSF of 9.8067. However, Strophanthidin formed 3 hydrogen bonds with the target at ILE21, GLY262 and LEU294, and induced a total RMSF of 5.4541 at Pocket 1. CONCLUSION: Overall, Isopteropodin and Strophanthidin were found to be better drug candidates than OOU and they showed potentials to inhibit the Brucella melitensis Methionyl-tRNA synthetase at Pocket 1, hence abilities to treat brucellosis. In-vivo and in-vitro investigations are needed to further evaluate the efficacy and toxicity of the lead compounds.