Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 402
Filter
Add filters

Document Type
Year range
1.
Drug Discov Ther ; 15(6): 281-288, 2021.
Article in English | MEDLINE | ID: covidwho-1622790

ABSTRACT

Coronavirus disease 2019 (COVID-19) has had a significant impact on human health and economic development over the past two years. Therapeutics in combination with vaccines are critical measures to fight the pandemic. The three areas of drug development are blocking the entry of SARS-CoV-2 into cells, suppressing viral replication inside cells, and regulating the immune system, and important advances have recently been made in those areas. Increasing numbers of neutralizing antibodies and small molecules that show promise have been fully approved or authorized for emergency use, resulting in decreased mortality of patients with COVID-19. The use of therapeutics will have a great impact on formulating and revising public policies to control the pandemic. The pace of lifting of restrictions and economic recovery worldwide will also accelerate in the future. Here, the drugs or agents that have attracted considerable attention and that have led to remarkable progress in the fight against COVID-19 are reviewed.


Subject(s)
COVID-19 , Drug Development , Drug Discovery , Humans , Pandemics , SARS-CoV-2
2.
AAPS J ; 24(1): 19, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1605878

ABSTRACT

Over the past decade, artificial intelligence (AI) and machine learning (ML) have become the breakthrough technology most anticipated to have a transformative effect on pharmaceutical research and development (R&D). This is partially driven by revolutionary advances in computational technology and the parallel dissipation of previous constraints to the collection/processing of large volumes of data. Meanwhile, the cost of bringing new drugs to market and to patients has become prohibitively expensive. Recognizing these headwinds, AI/ML techniques are appealing to the pharmaceutical industry due to their automated nature, predictive capabilities, and the consequent expected increase in efficiency. ML approaches have been used in drug discovery over the past 15-20 years with increasing sophistication. The most recent aspect of drug development where positive disruption from AI/ML is starting to occur, is in clinical trial design, conduct, and analysis. The COVID-19 pandemic may further accelerate utilization of AI/ML in clinical trials due to an increased reliance on digital technology in clinical trial conduct. As we move towards a world where there is a growing integration of AI/ML into R&D, it is critical to get past the related buzz-words and noise. It is equally important to recognize that the scientific method is not obsolete when making inferences about data. Doing so will help in separating hope from hype and lead to informed decision-making on the optimal use of AI/ML in drug development. This manuscript aims to demystify key concepts, present use-cases and finally offer insights and a balanced view on the optimal use of AI/ML methods in R&D.


Subject(s)
Artificial Intelligence , Clinical Trials as Topic , Computational Biology , Drug Development , Machine Learning , Pharmaceutical Research , Research Design , Animals , Artificial Intelligence/trends , Computational Biology/trends , Diffusion of Innovation , Drug Development/trends , Forecasting , Humans , Machine Learning/trends , Pharmaceutical Research/trends , Research Design/trends
3.
PLoS Pathog ; 17(12): e1010106, 2021 12.
Article in English | MEDLINE | ID: covidwho-1598647

ABSTRACT

The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies. We outline multidisciplinary approaches and technological innovations that need to be harnessed in order to improve preparedeness to the next pandemic.


Subject(s)
COVID-19/virology , Influenza, Human/virology , Orthomyxoviridae/physiology , SARS-CoV-2/physiology , Animals , Antiviral Agents , COVID-19/therapy , COVID-19/transmission , Drug Development , Evolution, Molecular , Humans , Influenza, Human/therapy , Influenza, Human/transmission , Orthomyxoviridae/immunology , SARS-CoV-2/immunology , Selection, Genetic , Viral Load , Viral Vaccines
4.
Turk J Med Sci ; 51(SI-1): 3139-3149, 2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1595702

ABSTRACT

Mobilizing the research ecosystem for accelerating vaccine and drug development has been an important reality of the pandemic. This article reviews the scientific advances that are attained by the COVID-19 Turkey Platform for vaccine and drug development against the SARS-CoV-2 virus. The platform that is coordinated by the Scientific and Technological Research Council of Turkey is established with a "co-creation and succeeding together" approach, which involves 436 researchers across 49 different institutions working on 17 vaccine and drug development projects in total. Recent advances of the COVID-19 Turkey Platform include the fourth virus-like particle-based vaccine candidate in the world to enter clinical studies based on the World Health Organization COVID-19 vaccine tracker that is currently completing phase 2 clinical studies on the path towards initiating phase 3 clinical studies. Moreover, an adjuvanted inactivated vaccine candidate and two drug candidates that have been identified through the virtual scanning of more than 20,000 molecules are currently in clinical studies. Other vaccines and drug candidates involve additional innovative aspects, and a locally synthesized drug is found to have an impact on COVID-19. This review article discusses the advances that are achieved by the COVID-19 Turkey Platform from the ecosystem perspective, emphasizing the important scientific advances that have been achieved in the field of medical sciences.


Subject(s)
COVID-19 Vaccines , COVID-19/prevention & control , Drug Development , Humans , SARS-CoV-2 , Turkey
5.
Int J Mol Sci ; 22(24)2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1572492

ABSTRACT

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug-drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/genetics , Drug-Related Side Effects and Adverse Reactions/metabolism , Pharmacogenetics/trends , Biomarkers , COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Central Nervous System Diseases/drug therapy , Cost-Benefit Analysis , Drug Development , Genotype , Humans , Neoplasms/drug therapy , Pharmaceutical Preparations , Pharmacogenetics/methods , Phenotype
6.
Ind Health ; 59(5): 293-297, 2021 Oct 05.
Article in English | MEDLINE | ID: covidwho-1547177

ABSTRACT

This paper reviews three viewpoints regarding the society after the COVID-19 infection on the concept of safety management. The first is the relationship between With COVID-19 and a zero risk. As a result of coexistence with COVID-19 for more than one year, the Japanese society thought that a zero risk is difficult to accomplish, and some risks will be accepted to maintain social activities. This leads a change in a way of thinking from zero risk to risk-based safety management. The second is the change in the way of working. As a result of having experienced remote work forcibly, it will become the hybrid model that incorporated remote work in a conventional method. Personnel evaluation changes from the seniority system to the job evaluation type, and each person's professional ability will be more focused on. The third is the review of the Japanese society system. In Japan, although the infection level was controlled to some extent by the groupism of the self-restraint of actions by mutual monitoring, there is a limit of managing based on groupism. Moreover, as seen in the delay of vaccine development and the medical care collapse, these problems should be improved by changing Japanese society system.


Subject(s)
COVID-19/epidemiology , Communicable Disease Control/organization & administration , Safety Management/organization & administration , Teleworking , COVID-19 Vaccines , Delivery of Health Care/organization & administration , Drug Development , Fukushima Nuclear Accident , Humans , Japan , Risk Assessment , SARS-CoV-2
8.
J Med Virol ; 94(1): 82-87, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544347

ABSTRACT

The rapid spread of the Delta variant suggests that SARS-CoV-2 will likely be rampant for months or years and could claim millions of more lives. All the known vaccines cannot well defeat SARS-CoV-2 due to their limited efficacy and production efficiency, except for the neglected live-attenuated vaccines (LAVs), which could have a much higher efficacy and much higher production efficiency than other vaccines. LAVs, like messiahs, have defeated far more pathogenic viruses than other vaccines in history, and most current human vaccines for viral diseases are safe LAVs. LAVs can block completely infection and transmission of relevant viruses and their variants. They can hence inhibit the emergence of vaccine-escape and virulence-enhancing variants and protect immunologically abnormal individuals better in general. The safety of COVID-19 LAVs, which could save millions of more lives, can be solidly guaranteed through animal experiments and clinical trials. The safety of COVID-19 LAVs could be greatly enhanced with intramuscular or oral administration, or administration along with humanized neutralizing monoclonal antibodies. Together, extensive global collaboration, which can greatly accelerate the development of safe COVID-19 LAVs, is imminently needed.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Drug Development , Humans , Mass Vaccination
12.
Clin Transl Sci ; 14(6): 2348-2359, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526356

ABSTRACT

Coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral infection, which can lead to pneumonia, lung injury, and death in susceptible populations. Understanding viral dynamics of SARS-CoV-2 is critical for development of effective treatments. An Immune-Viral Dynamics Model (IVDM) is developed to describe SARS-CoV-2 viral dynamics and COVID-19 disease progression. A dataset of 60 individual patients with COVID-19 with clinical viral load (VL) and reported disease severity were assembled from literature. Viral infection and replication mechanisms of SARS-CoV-2, viral-induced cell death, and time-dependent immune response are incorporated in the model to describe the dynamics of viruses and immune response. Disease severity are tested as a covariate to model parameters. The IVDM was fitted to the data and parameters were estimated using the nonlinear mixed-effect model. The model can adequately describe individual viral dynamics profiles, with disease severity identified as a covariate on infected cell death rate. The modeling suggested that it takes about 32.6 days to reach 50% of maximum cell-based immunity. Simulations based on virtual populations suggested a typical mild case reaches VL limit of detection (LOD) by 13 days with no treatment, a moderate case by 17 days, and a severe case by 41 days. Simulations were used to explore hypothetical treatments with different initiation time, disease severity, and drug effects to demonstrate the usefulness of such modeling in informing decisions. Overall, the IVDM modeling and simulation platform enables simulations for viral dynamics and treatment efficacy and can be used to aid in clinical pharmacokinetic/pharmacodynamic (PK/PD) and dose-efficacy response analysis for COVID-19 drug development.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Development/methods , Host Microbial Interactions/immunology , Models, Biological , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Cell Death/drug effects , Cell Death/immunology , Datasets as Topic , Dose-Response Relationship, Drug , Host Microbial Interactions/drug effects , Humans , Nonlinear Dynamics , SARS-CoV-2/drug effects , SARS-CoV-2/immunology , Severity of Illness Index , Treatment Outcome , Viral Load
13.
Pediatr Infect Dis J ; 41(1): e1-e5, 2022 01 01.
Article in English | MEDLINE | ID: covidwho-1522380

ABSTRACT

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.


Subject(s)
COVID-19/drug therapy , Research , Seizures/drug therapy , Child , Dosage Forms , Drug Compounding , Drug Development , Humans , Needs Assessment , Pharmaceutical Preparations , SARS-CoV-2
14.
Elife ; 92020 06 08.
Article in English | MEDLINE | ID: covidwho-1497819

ABSTRACT

SARS-CoV-2 presents an unprecedented international challenge, but it will not be the last such threat. Here, we argue that the world needs to be much better prepared to rapidly detect, define and defeat future pandemics. We propose that a Global Immunological Observatory and associated developments in systems immunology, therapeutics and vaccine design should be at the heart of this enterprise.


Subject(s)
Communicable Disease Control/organization & administration , Communicable Diseases, Emerging/prevention & control , Coronavirus Infections/epidemiology , Disaster Planning/organization & administration , Global Health , International Cooperation , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Population Surveillance , Animals , Anti-Infective Agents , COVID-19 , Climate Change , Cohort Studies , Communicable Disease Control/methods , Communicable Diseases, Emerging/diagnosis , Communicable Diseases, Emerging/epidemiology , Communicable Diseases, Emerging/immunology , Drug Development , Forecasting , Global Health/trends , Humans , Interdisciplinary Communication , Mass Screening/organization & administration , Models, Animal , Population Surveillance/methods , Serologic Tests , Vaccines , Weather , Zoonoses
15.
Mech Ageing Dev ; 199: 111551, 2021 10.
Article in English | MEDLINE | ID: covidwho-1492370

ABSTRACT

Polyphenols are chemopreventive through the induction of nuclear factor erythroid 2 related factor 2 (Nrf2)-mediated proteins and anti-inflammatory pathways. These pathways, encoding cytoprotective vitagenes, include heat shock proteins, such as heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1), as well as glutathione redox system to protect against cancer initiation and progression. Phytochemicals exhibit biphasic dose responses on cancer cells, activating at low dose, signaling pathways resulting in upregulation of vitagenes, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol (HT) or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Here, the importance of vitagenes in redox stress response and autophagy mechanisms, as well as the potential use of dietary antioxidants in the prevention and treatment of multiple types of cancer are discussed. We also discuss the possible relationship between SARS-CoV-2, inflammation and cancer, exploiting innovative therapeutic approaches with HT-rich aqueous olive pulp extract (Hidrox®), a natural polyphenolic formulation, as well as the rationale of Vitamin D supplementation. Finally, we describe innovative approaches with organoids technology to study human carcinogenesis in preclinical models from basic cancer research to clinical practice, suggesting patient-derived organoids as an innovative tool to test drug toxicity and drive personalized therapy.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Drug Development , NF-E2-Related Factor 2/metabolism , Organoids/drug effects , Oxidative Stress/drug effects , Polyphenols/pharmacology , Vitamin D/pharmacology , Animals , Antineoplastic Agents, Phytogenic/pharmacology , COVID-19/drug therapy , COVID-19/genetics , COVID-19/metabolism , COVID-19/virology , Humans , NF-E2-Related Factor 2/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Organoids/metabolism , Oxidation-Reduction , Oxidative Stress/genetics
17.
Mol Syst Biol ; 17(11): e10260, 2021 11.
Article in English | MEDLINE | ID: covidwho-1488874

ABSTRACT

Tremendous progress has been made to control the COVID-19 pandemic caused by the SARS-CoV-2 virus. However, effective therapeutic options are still rare. Drug repurposing and combination represent practical strategies to address this urgent unmet medical need. Viruses, including coronaviruses, are known to hijack host metabolism to facilitate viral proliferation, making targeting host metabolism a promising antiviral approach. Here, we describe an integrated analysis of 12 published in vitro and human patient gene expression datasets on SARS-CoV-2 infection using genome-scale metabolic modeling (GEM), revealing complicated host metabolism reprogramming during SARS-CoV-2 infection. We next applied the GEM-based metabolic transformation algorithm to predict anti-SARS-CoV-2 targets that counteract the virus-induced metabolic changes. We successfully validated these targets using published drug and genetic screen data and by performing an siRNA assay in Caco-2 cells. Further generating and analyzing RNA-sequencing data of remdesivir-treated Vero E6 cell samples, we predicted metabolic targets acting in combination with remdesivir, an approved anti-SARS-CoV-2 drug. Our study provides clinical data-supported candidate anti-SARS-CoV-2 targets for future evaluation, demonstrating host metabolism targeting as a promising antiviral strategy.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/therapeutic use , COVID-19/metabolism , Metabolic Networks and Pathways/genetics , Pandemics , SARS-CoV-2/physiology , Adenosine Monophosphate/therapeutic use , Alanine/therapeutic use , Animals , COVID-19/drug therapy , COVID-19/virology , Caco-2 Cells , Chlorocebus aethiops , Datasets as Topic , Drug Development , Drug Repositioning , Host-Pathogen Interactions , Humans , RNA, Small Interfering , Sequence Analysis, RNA , Vero Cells
18.
Molecules ; 26(20)2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1480883

ABSTRACT

Viral infections are among the most complex medical problems and have been a major threat to the economy and global health. Several epidemics and pandemics have occurred due to viruses, which has led to a significant increase in mortality and morbidity rates. Natural products have always been an inspiration and source for new drug development because of their various uses. Among all-natural sources, plant sources are the most dominant for the discovery of new therapeutic agents due to their chemical and structural diversity. Despite the traditional use and potential source for drug development, natural products have gained little attention from large pharmaceutical industries. Several plant extracts and isolated compounds have been extensively studied and explored for antiviral properties against different strains of viruses. In this review, we have compiled antiviral plant extracts and natural products isolated from plants reported since 2015.


Subject(s)
Antiviral Agents/isolation & purification , Antiviral Agents/pharmacology , Biological Products/pharmacology , Drug Development , Plant Extracts/pharmacology , Animals , Anti-HIV Agents/chemistry , Anti-HIV Agents/isolation & purification , Anti-HIV Agents/pharmacology , Antiviral Agents/chemistry , Biological Products/chemistry , Biological Products/isolation & purification , Drug Discovery , Flavivirus/drug effects , Hepatitis Viruses/drug effects , Humans , Molecular Structure , Orthomyxoviridae/drug effects , Plant Extracts/chemistry , Simplexvirus/drug effects
19.
Am J Bioeth ; 21(12): 4-19, 2021 12.
Article in English | MEDLINE | ID: covidwho-1475698

ABSTRACT

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask "where's our Operation Warp Speed?" and "why isn't Emergency Use Authorization an option for our health crises?" Although this pandemic bears a number of unique features, the response to COVID-19 offers translatable lessons, in both its successes and failures, for non-pandemic diseases. These include the importance of collaborating across sectors, supporting the highest-priority research efforts, adopting rigorous and innovative trial designs, and sharing reliable information quickly. In addition, the regulatory response to the pandemic demonstrates that lowering standards for marketing authorization can result in increased safety concerns, missed opportunities for research and treatment, and delays in determining what works. Accordingly, policymakers and patient advocates seeking to build on the COVID-19 experience for non-pandemic diseases with unmet treatment needs should focus their efforts on promoting robust and efficient research designs, improving access to clinical trials, and facilitating use of the Food and Drug Administration's existing Expanded Access pathway.


Subject(s)
COVID-19 , Pandemics , Drug Development , Humans , SARS-CoV-2
20.
Viruses ; 13(10)2021 10 18.
Article in English | MEDLINE | ID: covidwho-1471001

ABSTRACT

Advances in nanotechnology have enabled the development of a new generation of vaccines, which are playing a critical role in the global control of the COVID-19 pandemic and the return to normalcy. Vaccine development has been conducted, by and large, by countries in the global north. South Africa, as a major emerging economy, has made extensive investments in nanotechnology and bioinformatics and has the expertise and resources in vaccine development and manufacturing. This has been built at a national level through decades of investment. In this perspective article, we provide a synopsis of the investments made in nanotechnology and highlight how these could support innovation, research, and development for vaccines for this disease. We also discuss the application of bioinformatics tools to support rapid and cost-effective vaccine development and make recommendations for future research and development in this area to support future health challenges.


Subject(s)
COVID-19 Vaccines , COVID-19 , Nanotechnology , Computational Biology , Drug Development , Humans , Pandemics/prevention & control , South Africa
SELECTION OF CITATIONS
SEARCH DETAIL
...