In vitro and in silico evaluation of antiretrovirals against SARS-CoV-2: A drug repurposing approach.

Background: Drug repurposing is a valuable strategy for rapidly developing drugs for treating COVID-19. This study aimed to evaluate the antiviral effect of six antiretrovirals against SARS-CoV-2 in vitro and in silico. Methods: The cytotoxicity of lamivudine, emtricitabine, tenofovir, abacavir, efavirenz and raltegravir on Vero E6 was evaluated by MTT assay. The antiviral activity of each of these compounds was evaluated via a pre-post treatment strategy. The reduction in the viral titer was assessed by plaque assay. In addition, the affinities of the antiretroviral interaction with viral targets RdRp (RNA-dependent RNA polymerase), ExoN-NSP10 (exoribonuclease and its cofactor, the non-structural protein 10) complex and 3CLpro (3-chymotrypsin-like cysteine protease) were evaluated by molecular docking. Results: Lamivudine exhibited antiviral activity against SARS-CoV-2 at 200 µM (58.3%) and 100 µM (66.7%), while emtricitabine showed anti-SARS-CoV-2 activity at 100 µM (59.6%), 50 µM (43.4%) and 25 µM (33.3%). Raltegravir inhibited SARS-CoV-2 at 25, 12.5 and 6.3 µM (43.3%, 39.9% and 38.2%, respectively). The interaction between the antiretrovirals and SARS-CoV-2 RdRp, ExoN-NSP10 and 3CLpro yielded favorable binding energies (from -4.9 kcal/mol to -7.7 kcal/mol) using bioinformatics methods. Conclusion: Lamivudine, emtricitabine and raltegravir showed in vitro antiviral effects against the D614G strain of SARS-CoV-2. Raltegravir was the compound with the greatest in vitro antiviral potential at low concentrations, and it showed the highest binding affinities with crucial SARS-CoV-2 proteins during the viral replication cycle. However, further studies on the therapeutic utility of raltegravir in patients with COVID-19 are required.

Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro.

This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 µM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1 µM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1 µM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4 µM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of -6.7 kcal/mol and -7.5 kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19.

Design and evaluation of an online course to transfer suspected cases of COVID-19 from pharmacies-drugstores in Colombia

Introduction: it is needing to design, implement and evaluate the acceptance, relevance, and usability of an online course aimed at promoting the detection and referral of suspected cases of COVID-19 from pharmacies-drugstores. Method: the design of the course was based on a proposed route for the care of users suspected of COVID-19 attending pharmacies, complemented by information obtained through a search in PubMed/Medline and on Websites of leading organizations in the field. The information was structured in an online course, a formulary was developed and applied to assess the coverage, acceptability, and relevance of the course. Results: an online course (How do we act against COVID-19 from the drugstores?) was designed and organized in 7 units and with key concepts to identify and refer suspected cases of COVID-19 from pharmacies-drugstores, available in https://udearroba.udea.edu.co/externos/my/. From April/2020 to April/2021, 863 persons were registered, 382 (44.3%) finished and were sent the formulary for evaluation the course, which was returned by 240 (62.8%). In this group, the satisfaction with the course and education materials was 95.8% and 97.1%, respectively. Also, 97.9% people assert that the course contribute to identify and to refer suspected cases of COVID-19;and 93.3% that, the navigation through the course provides easy access of the contents. Conclusions: a virtual, open, and usable course is designed, implemented, and evaluated, and although the participants state that the course promoting the detection and referral of suspected cases of COVID-19, from pharmacies- drugstores, it is needing to conduct a study to assess this question. (English) [ FROM AUTHOR] Introducción: es necesario diseñar, implementar y evaluar la aceptación, pertinencia y usabilidad de un curso virtual orientado a favorecer la identificación y referenciación de casos sospechosos de COVID-19 desde farmacias- droguerías en Colombia. Método: el diseño del curso se fundamentó en una ruta propuesta para la atención de usuarios sospechosos de COVID- 19 que acuden a farmacias, complementada con información obtenida de una búsqueda en PubMed/Medline y en sitios Web de organizaciones referentes en el tema. La información se estructuró en un curso virtual, se elaboró y aplicó un instrumento para evaluar la cobertura, aceptabilidad y pertinencia del curso. Resultados: se diseñó el curso virtual ¿Cómo actuamos frente al COVID-19 desde las droguerías? organizado en 7 unidades con conceptos claves para identificar y referenciar casos sospechosos de COVID-19, desde farmacias-droguerías, disponible en https://udearroba.udea.edu.co/externos/my/. Entre abril/2020 y abril/2021 se registraron 863 personas, 382 (44,3%) finalizaron el curso y se les envió el instrumento de evaluación, y fue regresado por 240 (62,8%). En este grupo, la satisfacción con el curso y material didáctico fue del 95,8% y 97,1%, respectivamente. Además, el 97,9% manifestó que el curso contribuye a identificar y referenciar casos sospechosos de COVID-19;y el 93,3% que, el acceso y navegación por el curso, resultó sencillo. Conclusiones: se diseña, implementa y evalúa un curso virtual, abierto y usable, orientado a favorecer la identificación y referenciación de casos sospechosos de COVID-19, desde las farmacias-droguerías y, aunque los participantes declaran que contribuye con dicha finalidad, se requiere de un estudio diseñado para valorar esta aportación. (Spanish) [ FROM AUTHOR] Copyright of Ars Pharmaceutica is the property of Facultad de Farmacia de Granada and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Pharmacist's Role and Pharmaceutical Care During the COVID-19 Pandemic.

Pharmacists play a vital role in public health during the COVID-19 pandemic. In this chapter, we present the most significant contributions that pharmacists could make to communitarian and hospital settings. It includes the provision of essential services, such as continuous access to medication and supplies, support to medical services, education and information to the population and the health team to reduce the misuse of medications, patient monitoring and follow-up, and the detection and referral of suspected cases of COVID-19. The chapter ends with a discussion over certain elements related to innovation needs, such as telepharmacy services.

How to link patients with suspicious COVID-19 to health system from the community pharmacies? A route proposal.

Colombia confirmed its first case of the COVID-19 on March 6th, 2020. On March 16th, 2020, 54 cases have been confirmed (36 imported and 18 associated), therefore, Colombia is at highest alert, and it is now trying to avoid or minimize the last stage of "community transmission". We present a route proposal that shows how the community pharmacist may develop his responsibility to contribute to the early detection and appropriate referral of possible cases of the COVID-19. In the route have been considered three possible entrances depending on the needs of the users: anti-flu drugs, symptoms related to COVID-19 infection or the request for items for hygiene and prevention of transmission such as alcohol and face masks. Later, self-care education should be given, and the possible cases should be reported to the telephone lines designated by the mayor or the governor, continuing the healthcare process. Community pharmacies and pharmacy staff play a crucial role in minimizing the stage of "community transmission" of COVID-19, through properly detection and management of possible cases and customer education.