Can Costus afer be used for co-treatment of COVID-19, its symptoms and comorbidities? A novel approach for combating the pandemic and implications for sub-Saharan Africa

@#Despite the huge loss of lives and massive disruption of the world economy by the COVID-19 pandemic caused by SARS-CoV-2, scientists are yet to come out with an effective therapeutic against this viral disease. Several vaccines have obtained ‘emergency approval’, but difficulties are being faced in the even distribution of vaccines amongst high- and lowincome countries. On top of it, comorbidities associated with COVID-19 like diabetes, hypertension and malaria can seriously impede the treatment of the main disease, thus increasing the fatality rate. This is more so in the context of sub-Saharan African and south Asian countries. Our objective was to demonstrate that a single plant containing different phytoconstituents may be used for treatment of COVID-19 and comorbidities. Towards initial selection of a plant, existing scientific literature was scanned for reported relevant traditional uses, phytochemicals and pharmacological activities of a number of plants and their phytoconstituents pertaining to treatment of COVID-19 symptoms and comorbidities. Molecular docking studies were then performed with phytochemicals of the selected plant and SARS-CoV-2 components – Mpro, and spike protein receptor binding domain and hACE2 interface using AutoDock Vina. We showed that crude extracts of an indigenous African plant, Costus afer having traditional antidiabetic and antimalarial uses, has phytochemicals with high binding affinities for Mpro, and/or spike protein receptor binding domain and hACE2 interface; the various phytochemicals with predicted high binding energies include aferoside C, dibutyl phthalate, nerolidol, suginal, and ±-terpinene, making them potential therapeutics for COVID-19. The results suggest that crude extracts and phytochemicals of C. afer can function as a treatment modality for COVID-19 and comorbidities like especially diabetes and malaria.

Potential role of flavonoids against SARS-CoV-2 induced diarrhea

@#COVID-19, caused by the SARS-CoV-2 virus, can lead to massive inflammation in the gastrointestinal tract causing severe clinical symptoms. SARS-CoV-2 infects lungs after binding its spike proteins with alveolar angiotensin-converting enzyme 2 (ACE2), and it also triggers inflammation in the gastrointestinal tract. SARS-CoV-2 invades the gastrointestinal tract by interacting with Toll-like receptor-4 (TLR4) that induces the expression of ACE2. The influx of ACE2 facilitates cellular binding of more SARS-CoV-2 and causes massive gastrointestinal inflammation leading to diarrhea. Diarrhea prior to COVID-19 infection or COVID-19-induced diarrhea reportedly ends up in a poor prognosis for the patient. Flavonoids are part of traditional remedies for gastrointestinal disorders. Preclinical studies show that flavonoids can prevent infectious diarrhea. Recent studies show flavonoids can inhibit the multiplication of SARS-CoV-2. In combination with vitamin D, flavonoids possibly activate nuclear factor erythroid-derived-2-related factor 2 that downregulates ACE2 expression in cells. We suggest that flavonoids have the potential to prevent SARS-CoV-2 induced diarrhea.

In silico screening of Allium cepa phytochemicals for their binding abilities to SARS and SARS-CoV-2 3C-like protease and COVID-19 human receptor ACE-2

@# Corona virus SARS-CoV-2-induced viral disease (COVID-19) is a zoonotic disease that was initially transmitted from animals to humans. The virus surfaced towards the end of December 2019 in Wuhan, China where earlier SARS (Severe Acute Respiratory Syndrome) had also surfaced in 2003. Unlike SARS, SARS-CoV-2 (a close relative of the SARS virus) created a pandemic, and as of February 24 2021, caused 112,778,672 infections and 2,499,252 deaths world-wide. Despite the best efforts of scientists, no drugs against COVID-19 are yet in sight; five vaccines have received emergency approval in various countries, but it would be a difficult task to vaccinate twice the world population of 8 billion. The objective of the present study was to evaluate through in silico screening a number of phytochemicals in Allium cepa (onion) regarding their ability to bind to the main protease of COVID-19 known as the 3C-like protease or 3CLpro, (PDB ID: 6LU7), 3CLpro of SARS (PDB ID: 3M3V), and human angiotensin converting enzyme-2 (ACE-2), [PDB ID: 1R42], which functions as a receptor for entry of the virus into humans. Molecular docking (blind docking, that is docking not only against any target pocket) were done with the help of AutoDockVina. It was observed that of the twenty-two phytochemicals screened, twelve showed good binding affinities to the main protease of SARS-CoV-2. Surprisingly, the compounds also demonstrated good binding affinities to ACE-2. It is therefore very likely that the binding affinities shown by these compounds against both 3CLpro and ACE-2 merit further study for their potential use as therapeutic agents.

Diagnostic Accuracy of Imprint Cytology and Frozen Section for CNS Tumor.

The present study was a cross-sectional type of descriptive one carried out with the objective of determining the diagnostic accuracy of imprint cytology and frozen section of central nervous system tumors. A purposively selected sample of 33 clinically diagnosed patients with CNS tumors has been included for the study. The relevant data on CNS tumors were collected by using imprint cytology, frozen section and paraffin section. The sensitivity of imprint cytology was 75.0% and specificity was 55.17% respectively. On the other hand positive predictive value of imprint cytology was 18.75% and negative predictive value was 94.11%. The sensitivity of frozen section was 100% and specificity was 86.21% respectively. Comparing the findings of the frozen section to histopathology, the positive predictive value was 50.0% and negative predictive value was 100%. The sensitivity and specificity of imprint cytology was lower in comparison to frozen section and paraffin section. Still then imprint cytology is preferred, because it can be carried out rapidly and easily. It will also be a very helpful aid especially when facilities for frozen section are limited but neurosurgical-procedure is available. A well designed research with adequate sample size should be carried out to get better diagnostic accuracy of imprint cytology in central nervous system tumors.

Noninvasive Estimation of PCWP with Doppler Transmitral Flow Velocity Pattern in Patients with Coronary Artery Disease.

Background: Pulmonary capillary wedge pressure is an important clinical marker of cardiac function. Recent studies have demonstrated Doppler transmitral flow velocity pattern could be useful in assessing PCWP no invasively in patient with known heart disease. Objective: The aims of the study were to correlate the Pulmonary Capillary Wedge Pressure (PCWP) estimated by Doppler echocardiography with that obtained at cardiac catheterization and to evaluate the feasibility and accuracy of Doppler echocardiographic data. Method: All patients underwent simultaneous cardiac catheterization and were studied by Doppler echocardiography. Mitral flow velocity variables & maximal left atrial volume (MLAV) were correlated with invasive PCWP by both single & multilinear regression analysis. Result: A statistically significant negative correlation of deceleration time (r=-0.483; p=0.001) and ejection fraction (r=-0.334; p=0.01) and a statistically significant positive correlation of peak E wave (r=0.345; p=0.01) and deceleration rate (r=0.651; p=0.001 were found with catheter derived PCWP. Multiple regression analysis was used to derive an equation for noninvasive estimation of PCWP. Equation. With 2-D Echo + Mitral flow variables: PCWP = 1.43 X DR + 1.32 X E/A – 0.024 X DT + .02 X MLAV + 9.2. Conclusion: The correlation coefficient between measured and estimated PCWP from the equation was (r=0.678). Data indicated that in patients with CAD the noninvasive assessment of transmitral flow velocity pattern by Doppler echocardiography could predict PCWP with a clinically meaningful degree of accuracy.