Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit cytopathic effect, papain-like protease, and MPRO enzymes of SARS-CoV-2.

Background: Although tremendous success has been achieved in the development and deployment of effective COVID-19 vaccines, developing effective therapeutics for the treatment of those who do come down with the disease has been with limited success. To repurpose existing drugs for COVID-19, we previously showed, qualitatively, that erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin inhibit SARS-COV-2-induced cytopathic effect (CPE) in Vero cells. Aim: This study aimed to quantitatively explore the inhibition of SARS-CoV-2-induced CPE by erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin and to determine the effect of these drugs on SARS-CoV-2 papain-like protease and 3CL protease (MPRO) enzymes. Methods: Neutral red (3-amino-7-dimethylamino-2-methyl-phenazine hydrochloride) cell viability assay was used to quantify CPE after infecting pre-treated Vero cells with clinical SARS-Cov-2 isolates. Furthermore, SensoLyte® 520 SARS-CoV-2 papain-like protease and SensoLyte® 520 SARS-CoV-2 MPRO activity assay kits were used to evaluate the inhibitory activity of the drugs on the respective enzymes. Results: Erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibit SARS-CoV-2-induced CPE in Vero cells, with inhibitory concentration-50 (IC50) values of 3.27 µM, 4.23 µM, 9.29 µM, 3.19 µM, and 84.31 µM, respectively. Furthermore, erythromycin, retapamulin, pyridoxine, folic acid, and ivermectin dose-dependently inhibited SARS-CoV-2 papain-like protease with IC50 values of 0.94 µM, 0.88 µM, 1.14 µM, 1.07 µM, and 1.51 µM, respectively, and inhibited the main protease (MPRO) with IC50 values of 1.35 µM, 1.25 µM, 7.36 µM, 1.15 µM, and 2.44 µM, respectively. Conclusion: The IC50 for all the drugs, except ivermectin, was at the clinically achievable plasma concentration in humans, which supports a possible role for the drugs in the management of COVID-19. The lack of inhibition of CPE by ivermectin at clinical concentrations could be part of the explanation for its lack of effectiveness in clinical trials.

Innovative, rapid, high-throughput method for drug repurposing in a pandemic-A case study of SARS-CoV-2 and COVID-19.

Several efforts to repurpose drugs for COVID-19 treatment have largely either failed to identify a suitable agent or agents identified did not translate to clinical use. Reasons that have been suggested to explain the failures include use of inappropriate doses, that are not clinically achievable, in the screening experiments, and the use of inappropriate pre-clinical laboratory surrogates to predict efficacy. In this study, we used an innovative algorithm, that incorporates dissemination and implementation considerations, to identify potential drugs for COVID-19 using iterative computational and wet laboratory methods. The drugs were screened at doses that are known to be achievable in humans. Furthermore, inhibition of viral induced cytopathic effect (CPE) was used as the laboratory surrogate to predict efficacy. Erythromycin, pyridoxine, folic acid and retapamulin were found to inhibit SARS-CoV-2 induced CPE in Vero cells at concentrations that are clinically achievable. Additional studies may be required to further characterize the inhibitions of CPE and the possible mechanisms.

Gender Variations in Pharmacokinetics of Paracetamol in Hausa/Fulani Ethnic group in Northwest Nigeria - A Two-stage Approach.

BACKGROUND: Paracetamol is one of the most commonly used drugs worldwide and has been linked to drug-related liver damage, even when taken at recommended doses. Ingesting the upper limit of recommended doses of the drug produced a doubling of mortality when compared to not taking the drug. Acetaminophen ingestion has been implicated in the development of angioedema, the exasperation of asthma, and urticaria in patients with aspirin intolerance. AIM: This study aimed at assessing gender variations in the pharmacokinetics of paracetamol in Hausa/Fulani, the most populous ethnic group in Nigeria and determines a possibility of toxicity in the group. METHODS: It was an exploratory study involving twenty participants selected by criterion sampling who satisfied inclusion criteria. They were fasted 11-h preceding acetaminophen administration to 3 h after administration. A single dose of acetaminophen, 1 g orally with 300 ml of distilled water, was administered at 8 A. M. Blood was obtained before the administration and 15, 30, and 45 min, and 1, 2, 3, 4, 5, and 6 h after the administration. Acetaminophen plasma concentrations were determined by validated reverse-phase high-performance liquid chromatography Food and Drug Administration guidelines. RESULTS: Six out of 19 (31.6%) participants have higher than maximum therapeutic plasma concentration (>20 µg/ml). Pharmacokinetics parameters were higher in males except for clearance and volume of distribution. CONCLUSION: Clearance from the plasma tends to be more for females than their male counterparts. A good proportion of Hausa/Fulani is prone to acetaminophen toxicity at a therapeutic dose.

Epidemiological comparison of the first and second waves of the COVID-19 pandemic in Nigeria, February 2020-April 2021.

BACKGROUND: With reports of surges in COVID-19 case numbers across over 50 countries, country-level epidemiological analysis is required to inform context-appropriate response strategies for containment and mitigation of the outbreak. We aimed to compare the epidemiological features of the first and second waves of COVID-19 in Nigeria. METHODS: We conducted a retrospective analysis of the Surveillance Outbreak Response Management and Analysis System data of the first and second epidemiological waves, which were between 27 February and 24 October 2020, and 25 October 2020 to 3 April 2021, respectively. Descriptive statistical measures including frequencies and percentages, test positivity rate (TPR), cumulative incidence (CI) and case fatality rates (CFRs) were compared. A p value of <0.05 was considered statistically significant. All statistical analyses were carried out in STATA V.13. RESULTS: There were 802 143 tests recorded during the study period (362 550 and 439 593 in the first and second waves, respectively). Of these, 66 121 (18.2%) and 91 644 (20.8%) tested positive in the first and second waves, respectively. There was a 21.3% increase in the number of tests conducted in the second wave with TPR increasing by 14.3%. CI during the first and second waves were 30.3/100 000 and 42.0/100 000 respectively. During the second wave, confirmed COVID-19 cases increased among females and people 30 years old or younger and decreased among urban residents and individuals with travel history within 14 days of sample collection (p value <0.001). Most confirmed cases were asymptomatic at diagnosis during both waves: 74.9% in the first wave; 79.7% in the second wave. CFR decreased during the second wave (0.7%) compared with the first wave (1.8%). CONCLUSION: Nigeria experienced a larger but less severe second wave of COVID-19. Continued implementation of public health and social measures is needed to mitigate the resurgence of another wave.

Attitude of nurses and pharmacists on adverse drug reactions reporting in selected hospitals in Sokoto, Northwest Nigeria.

OBJECTIVE: Objective of this study was to assess the attitude of nurses and pharmacists towards adverse drug reactions (ADRs) reporting. METHODS: The questionnaire was designed based on extended "Inman seven deadly sins." Two hundred and seventy-two respondents were selected by stratified sampling technique. The questionnaires were delivered to the respondents at their places of practice. The data generated were analyzed by Sigma XL Software Inc. FINDINGS: There was no statistically significant relationship between demographic profiles and reporting attitude except for qualification. On extended "Inman seven deadly sins" awareness of reporting protocol and nearby center for ADRs reporting were low 27.3 and 7.5%, respectively. However, respondents' score on components of attitude of ADRs reporting is generally encouraging. On comparative basis, no statistical significance exists between pharmacists and nurses. CONCLUSION: The study showed that attitude of respondents towards ADRs reporting is good. However, there is a need for targeted health education intervention among these cadres of health-care professionals, especially on aspects of awareness of reporting protocol and reporting center.

Knowledge and attitudes of physicians relating to reporting of adverse drug reactions in Sokoto, north-western Nigeria.

BACKGROUND/OBJECTIVES: Adverse drug reactions (ADRs) are important causes of morbidities. Voluntary reporting of ADR is important in safety surveillance of medicines already in the market. This study was, therefore, conducted to appraise the current documentation of ADR in Sokoto, to analyze the extent to which clinicians appreciate factors that could affect reporting ADRs. MATERIALS AND METHODS: Four hospitals within Sokoto metropolis were selected by convenient sampling. Pre-validated questionnaires containing questions on demographic and professional characteristics, and questions that evaluate attitudes as listed in the so-called "deadly sins" of Inman were self-administered by physicians. Data from respondents were analyzed by logistic regression. RESULTS: Of 61 physicians interviewed, 43 (70.5%) had encountered potential ADRs in the 12 months before the study but only 3 (7.0%) of these were reported. Fifty eight (95.1%) of the respondents were not aware that an ADR reporting system was available in Sokoto but all the 3 respondents who were aware of the existence of a reporting system had reported an ADR. Generally, there was no significant relationship between demographic and professional attributes and scores obtained on each of the Inman's attitude measured except that more experienced physicians tend to believe that ADRs are not impossible to identify and female physicians were more reluctant to engage representatives of pharmaceutical companies on ADRs related to their drugs. Additional attitudes that may influence ADRs reporting were identified. CONCLUSION: Adverse drug reactions are under-reported in Sokoto. Lack of physicians' awareness of channels for reporting appears to be the major cause.

Antihyperglycaemic activity of aqueous leaf extract of Combretum micranthum (Combretaceae) in normal and alloxan-induced diabetic rats.

AIM OF THE STUDY: To investigate antidiabetic effect of the leaves of Combretum micranthum G. Don, a medicinal plant used for treating diabetes in Northwestern Nigeria. MATERIALS AND METHODS: Three doses (100mg/kg, 200mg/kg and 400mg/kg) of the aqueous leaf extract of Combretum micranthum were administered to normal glucose loaded, subdiabetic and diabetic rats. RESULTS: Of the doses tested, 100mg/kg of the extract was the most effective. It produces a significant hypoglycaemic and antidiabetic activity comparable to the effect of standard drug (0.6 mg/kg glibenclemide). CONCLUSION: This study demonstrated the potential antidiabetic property of aqueous leaf extract of Combretum micranthum thus justifying its traditional usage.