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1.
Phytother Res ; 35(7): 3447-3483, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1323905

ABSTRACT

The pandemic of viral diseases like novel coronavirus (2019-nCoV) prompted the scientific world to examine antiviral bioactive compounds rather than nucleic acid analogous, protease inhibitors, or other toxic synthetic molecules. The emerging viral infections significantly associated with 2019-nCoV have challenged humanity's survival. Further, there is a constant emergence of new resistant viral strains that demand novel antiviral agents with fewer side effects and cell toxicity. Despite significant progress made in immunization and regenerative medicine, numerous viruses still lack prophylactic vaccines and specific antiviral treatments that are so often influenced by the generation of viral escape mutants. Of importance, medicinal herbs offer a wide variety of therapeutic antiviral chemotypes that can inhibit viral replication by preventing viral adsorption, adhering to cell receptors, inhibiting virus penetration in the host cell, and competing for pathways of activation of intracellular signals. The present review will comprehensively summarize the promising antiviral activities of medicinal plants and their bioactive molecules. Furthermore, it will elucidate their mechanism of action and possible implications in the treatment/prevention of viral diseases even when their mechanism of action is not fully understood, which could serve as the base for the future development of novel or complementary antiviral treatments.


Subject(s)
Antiviral Agents , Plants, Medicinal , Virus Diseases , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19 , Humans , Plants, Medicinal/chemistry , Virus Diseases/drug therapy
2.
ISA Trans ; 124: 21-30, 2022 May.
Article in English | MEDLINE | ID: covidwho-1237731

ABSTRACT

The COVID-19 outbreak is an epidemic disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When a new virus emerges, generally, little is known about it, and no vaccines or other pharmaceutical interventions are available. In the case of a person-to-person transmission virus with no vaccines or other pharmaceutical interventions, the only way to control the virus outbreak is by keeping a sustained physical distancing between the individuals. However, to adjust the level of the physical distancing accurately can be so complicated. Any level above the necessary can compromise the economic activity, and any level below can collapse the health care system. This work proposes a controller to keep the number of hospitalized individuals below a limit, and a new group-structured model to describe the COVID-19 outbreak. The proposed controller is robust to the uncertainties in the parameters of the model and keeps the number of infected individuals controlled only by adjusting the social distancing level. Numerical simulations, to show the behavior of the proposed controller and model, are done.


Subject(s)
COVID-19 , Epidemics , COVID-19/epidemiology , COVID-19/prevention & control , Epidemics/prevention & control , Humans , Pharmaceutical Preparations , Physical Distancing , SARS-CoV-2
3.
Bol Med Hosp Infant Mex ; 78(1): 66-74, 2021.
Article in English | MEDLINE | ID: covidwho-1116360

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) pandemic has posed significant challenges globally. Continuous transmission of the virus is mostly due to insufficient infection control measures and a lack of vaccines. Therefore, this review aimed to identify and describe possible vaccines for the prevention of COVID-19. Methods: A systematic review of the scientific literature was performed through electronic searches of the main databases to identify published reports or studies on vaccines under development against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Websites from international organizations, institutes of health and research, Google, and references from identified studies were also reviewed. Studies examining the mechanisms of infection, immunopathology, and genomics were excluded. Results: A total of 141 vaccines in development against SARS-CoV-2 were identified. The technologies used include weakened and inactive viruses, viral vectors, nucleic acids, and proteins. So far, 13 vaccines (9.2%) are under clinical evaluation; only the AZD1222 vaccine is under clinical evaluation Phase II-III. Ad5-nCoV and mRNA-1273 vaccines showed to produce neutralizing antibodies and also to be safe. Conclusions: Despite efforts invested in developing SARS-CoV-2 vaccines, more research is still required. The vaccine developers, international health organizations, and the decision-makers of health policies must carry out conjunct cooperation to face the different challenges and guarantee the development of an effective vaccine.


Introducción: La pandemia de COVID-19 ha planteado grandes retos en todo el mundo. La transmisión continua del virus se debe, en gran parte, a las medidas deficientes para el control de infecciones y a la falta de vacunas. El objetivo de esta revisión fue identificar y describir las posibles vacunas para la prevención de la COVID-19. Métodos: Se realizó una revisión sistemática de la literatura científica mediante búsquedas en las principales bases de datos electrónicas, para identificar informes o estudios publicados sobre las vacunas en proceso de desarrollo contra el SARS-CoV-2. También se revisaron páginas web de organismos internacionales, institutos de salud e investigación, Google y las referencias de los estudios identificados. Se excluyeron los estudios que examinaron los mecanismos de infección, inmunopatológicos y de genómica. Resultados: En total se identificaron 141 vacunas en desarrollo contra el SARS-CoV-2. Las tecnologías utilizadas incluyen virus debilitados e inactivos, vectores virales, ácidos nucleicos y proteínas. Hasta el momento solo 13 vacunas (9.2%) se encuentran en proceso de evaluación clínica y solo la vacuna AZD1222 se encuentra en fase II-III. Las vacunas Ad5-nCoV y mRNA-1273 han mostrado producción de anticuerpos neutralizantes, además de ser seguras. Conclusiones: A pesar de los esfuerzos invertidos para el desarrollo de vacunas contra el SARS-CoV-2, aún se requiere más investigación. Es necesario que los desarrolladores de vacunas, los organismos internacionales de salud y los tomadores de decisiones de políticas sanitarias cooperen para afrontar los diferentes desafíos y garantizar el desarrollo de una vacuna eficaz.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , 2019-nCoV Vaccine mRNA-1273 , Animals , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , ChAdOx1 nCoV-19 , Health Policy , Humans
4.
Curr Pharm Des ; 26(41): 5300-5309, 2020.
Article in English | MEDLINE | ID: covidwho-1073205

ABSTRACT

BACKGROUND: Previously human society has faced various unprecedented pandemics in the history and viruses have majorly held the responsibilities of those outbreaks. Furthermore, due to amplified global connection and speedy modernization, epidemic outbreaks caused by novel and re-emerging viruses signify potential risk to community health. Despite great advancements in immunization and drug discovery processes, various viruses still lack prophylactic vaccines and efficient antiviral therapies. Although, vaccine is a prophylaxes option, but it cannot be applied to infected patients, hence therapeutic interventions are urgently needed to control the ongoing global SARS- CoV-2 pandemic condition. To spot the novel antiviral therapy is of decisive importance and Mother Nature is an excellent source for such discoveries. METHODOLOGY: In this article, prompt high through-put virtual screening for vetting the best possible drug candidates from natural compounds' databases has been implemented. Herein, time tested rigorous multi-layered drug screening process to narrow down 66,969 natural compounds for the identification of potential lead(s) is implemented. Druggability parameters, different docking approaches and neutralization tendency of the natural products were employed in this study to screen the best possible natural compounds from the digital libraries. CONCLUSION: The results of this study conclude that compounds PALA and HMCA are potential inhibitors of SARS-CoV-2 spike protein and can be further explored for experimental validation. Overall, the methodological approach reported in this article can be suitably used to find the potential drug candidates against SARS-CoV2 in the burning situation of COVID-19 with less expenditure and a concise span of time.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Wellcome Open Res ; 5: 141, 2020.
Article in English | MEDLINE | ID: covidwho-895726

ABSTRACT

Background: COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or therapeutic agent to treat COVID-19. This clinical trial is designed to evaluate chloroquine as a potential therapeutic for the treatment of hospitalised people with COVID-19. We hypothesise that chloroquine slows viral replication in patients with COVID-19, attenuating the infection, and resulting in more rapid decline of viral load in throat/nose swabs. This viral attenuation should be associated with improved patient outcomes. Method: The study will start with a 10-patient prospective observational pilot study following the same entry and exclusion criteria as for the randomized trial and undergoing the same procedures. The main study is an open label, randomised, controlled trial with two parallel arms of standard of care (control arm) versus standard of care with 10 days of chloroquine (intervention arm) with a loading dose over the first 24 hours, followed by 300mg base orally once daily for nine days. The study will recruit patients in three sites in Ho Chi Minh City, Vietnam: the Hospital for Tropical Diseases, the Cu Chi Field Hospital, and the Can Gio COVID hospital. The primary endpoint is the time to viral clearance from throat/nose swab, defined as the time following randomization until the midpoint between the last positive and the first of the negative throat/nose swabs. Viral presence will be determined using RT-PCR to detect SARS-CoV-2 RNA. Discussion: The results of the study will add to the evidence-based guidelines for management of COVID-19. Given the enormous experience of its use in malaria chemoprophylaxis, excellent safety and tolerability profile, and its very low cost, if proved effective then chloroquine would be a readily deployable and affordable treatment for patients with COVID-19. Trial registration: Clinicaltrials.gov NCT04328493 31/03/2020.

6.
EMBO J ; 39(21): e106057, 2020 11 02.
Article in English | MEDLINE | ID: covidwho-846583

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Cholesterol/metabolism , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Respiratory Mucosa/virology , Steroid Hydroxylases/pharmacology , Virus Internalization/drug effects , Acetyl-CoA C-Acetyltransferase/metabolism , Animals , COVID-19 , Cell Line , Cell Membrane/drug effects , Cell Membrane/metabolism , Chlorocebus aethiops , Enzyme Activation/drug effects , Humans , Middle East Respiratory Syndrome Coronavirus/drug effects , Organoids/virology , Pandemics , Respiratory Mucosa/drug effects , SARS-CoV-2 , Vero Cells
7.
Cell ; 181(4): 865-876.e12, 2020 05 14.
Article in English | MEDLINE | ID: covidwho-684968

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has highlighted the need for antiviral approaches that can target emerging viruses with no effective vaccines or pharmaceuticals. Here, we demonstrate a CRISPR-Cas13-based strategy, PAC-MAN (prophylactic antiviral CRISPR in human cells), for viral inhibition that can effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus (IAV) in human lung epithelial cells. We designed and screened CRISPR RNAs (crRNAs) targeting conserved viral regions and identified functional crRNAs targeting SARS-CoV-2. This approach effectively reduced H1N1 IAV load in respiratory epithelial cells. Our bioinformatic analysis showed that a group of only six crRNAs can target more than 90% of all coronaviruses. With the development of a safe and effective system for respiratory tract delivery, PAC-MAN has the potential to become an important pan-coronavirus inhibition strategy.


Subject(s)
Antiviral Agents/pharmacology , Betacoronavirus/drug effects , CRISPR-Cas Systems , Influenza A Virus, H1N1 Subtype/drug effects , RNA, Viral/antagonists & inhibitors , A549 Cells , Antibiotic Prophylaxis/methods , Base Sequence , Betacoronavirus/genetics , Betacoronavirus/growth & development , COVID-19 , Clustered Regularly Interspaced Short Palindromic Repeats , Computer Simulation , Conserved Sequence , Coronavirus/drug effects , Coronavirus/genetics , Coronavirus/growth & development , Coronavirus Infections/drug therapy , Coronavirus Nucleocapsid Proteins , Coronavirus RNA-Dependent RNA Polymerase , Epithelial Cells/virology , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/growth & development , Lung/pathology , Lung/virology , Nucleocapsid Proteins/genetics , Pandemics , Phosphoproteins , Phylogeny , Pneumonia, Viral/drug therapy , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2 , Viral Nonstructural Proteins/genetics
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