Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 52
Filter
1.
Nature ; 601(7894): 496, 2022 01.
Article in English | MEDLINE | ID: covidwho-1641925

Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Drug Development/trends , Drug Resistance, Viral , Research Personnel , SARS-CoV-2/drug effects , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Administration, Oral , Alanine/administration & dosage , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Antiviral Agents/supply & distribution , COVID-19/mortality , COVID-19/prevention & control , COVID-19 Vaccines/supply & distribution , Cytidine/administration & dosage , Cytidine/analogs & derivatives , Cytidine/pharmacology , Cytidine/therapeutic use , Drug Approval , Drug Combinations , Drug Resistance, Viral/drug effects , Drug Resistance, Viral/genetics , Drug Therapy, Combination , Hospitalization/statistics & numerical data , Humans , Hydroxylamines/administration & dosage , Hydroxylamines/pharmacology , Hydroxylamines/therapeutic use , Lactams/administration & dosage , Lactams/pharmacology , Lactams/therapeutic use , Leucine/administration & dosage , Leucine/pharmacology , Leucine/therapeutic use , Medication Adherence , Molecular Targeted Therapy , Mutagenesis , Nitriles/administration & dosage , Nitriles/pharmacology , Nitriles/therapeutic use , Proline/administration & dosage , Proline/pharmacology , Proline/therapeutic use , Public-Private Sector Partnerships/economics , Ritonavir/administration & dosage , Ritonavir/pharmacology , Ritonavir/therapeutic use , SARS-CoV-2/enzymology , SARS-CoV-2/genetics
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
5.
Drug Discov Today ; 26(10): 2209-2213, 2021 10.
Article in English | MEDLINE | ID: covidwho-1375052

ABSTRACT

The post-coronavirus era will open myriad opportunities for the biopharma industry. However, the extent to which each country will take advantage of this promising new scenario will largely depend on its position in a few key areas. Here, we offer an overview of the European countries that are winning and those that are lagging behind in the race to attract the greatest investment in this industry and to attain the highest rate of successful new ventures. Our results highlight the vital importance of a sound, active funding base, especially in terms of venture capital. Our findings also suggests that general scientific foundations are not enough to secure an advantage in new venture formation.


Subject(s)
COVID-19 , Drug Development/economics , Drug Development/trends , Drug Industry/economics , Drug Industry/trends , Investments , Pandemics , Europe , Foundations , Research
7.
Nat Med ; 27(3): 401-410, 2021 03.
Article in English | MEDLINE | ID: covidwho-1319040

ABSTRACT

The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease outbreaks. Emphasis should focus not only on the development of broad-spectrum small-molecule and antibody direct-acting antivirals, but also on host-factor therapeutics, including repurposing previously approved or in-pipeline drugs. Another new class of therapeutics with great antiviral therapeutic potential is RNA-based therapeutics. Rather than only focusing on known risks, dedicated efforts must be made toward pre-emptive research focused on outbreak-prone virus families, ultimately offering a strategy to shorten the gap between outbreak and response. Emphasis should also focus on orally available drugs for outpatient use, if possible, and on identifying combination therapies that combat viral and immune-mediated pathologies, extend the effectiveness of therapeutic windows and reduce drug resistance. While such an undertaking will require new vision, dedicated funding and private, federal and academic partnerships, this approach offers hope that global populations need never experience future pandemics such as COVID-19.


Subject(s)
Communicable Diseases, Emerging/therapy , Therapies, Investigational , Virus Diseases/therapy , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Drug Development/methods , Drug Development/trends , Drug Repositioning , History, 21st Century , Humans , Inventions/trends , Pandemics , SARS-CoV-2 , Therapies, Investigational/methods , Therapies, Investigational/trends
9.
Signal Transduct Target Ther ; 6(1): 177, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1298834

ABSTRACT

Rapid development of vaccines and therapeutics is necessary to tackle the emergence of new pathogens and infectious diseases. To speed up the drug discovery process, the conventional development pipeline can be retooled by introducing advanced in vitro models as alternatives to conventional infectious disease models and by employing advanced technology for the production of medicine and cell/drug delivery systems. In this regard, layer-by-layer construction with a 3D bioprinting system or other technologies provides a beneficial method for developing highly biomimetic and reliable in vitro models for infectious disease research. In addition, the high flexibility and versatility of 3D bioprinting offer advantages in the effective production of vaccines, therapeutics, and relevant delivery systems. Herein, we discuss the potential of 3D bioprinting technologies for the control of infectious diseases. We also suggest that 3D bioprinting in infectious disease research and drug development could be a significant platform technology for the rapid and automated production of tissue/organ models and medicines in the near future.


Subject(s)
Bioprinting/trends , Genetic Diseases, Inborn/therapy , Printing, Three-Dimensional/trends , Biomimetics/trends , Drug Development/trends , Drug Discovery/trends , Humans , Tissue Engineering/trends
10.
Pharmaceut Med ; 35(4): 197-202, 2021 07.
Article in English | MEDLINE | ID: covidwho-1293483

ABSTRACT

The medical affairs function represents one of the scientific interfaces in a pharmaceutical organization. Over the last two decades, medical affairs has evolved from being a support function to a strategic pillar within organizational business units. The COVID-19 pandemic has given rise to unforeseen circumstances resulting in a dramatic change in external stakeholder engagements, catapulting the medical affairs function into leading the way on scientific engagements and patient-centric endeavors. The changes in stakeholder interactions and behavior as a result of the pandemic last year are likely to persist in the foreseeable future for which medical affairs professionals need to enhance existing skill sets and acquire expertise in newer domains. In this paper, the transformation of the medical affairs team to a key strategic partner and the skills required to strengthen this transition, in the next normal of a post-COVID world, is explored.


Subject(s)
COVID-19/prevention & control , Drug Development/trends , Drug Industry/trends , Stakeholder Participation , COVID-19/epidemiology , Communicable Disease Control/standards , Drug Development/organization & administration , Drug Development/standards , Drug Industry/organization & administration , Drug Industry/standards , Health Services Accessibility/standards , Humans , India , Pandemics/prevention & control
11.
Biochem Pharmacol ; 189: 114424, 2021 07.
Article in English | MEDLINE | ID: covidwho-1269238

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Three viral proteins, the spike protein (S) for attachment of virus to host cells, 3-chymotrypsin-like cysteine protease (Mpro) for digestion of viral polyproteins to functional proteins, and RNA-dependent-RNA-polymerase (RdRp) for RNA synthesis are the most critical proteins for virus infection and replication, rendering them the most important drug targets for both antibody and chemical drugs. Due to its low-fidelity polymerase, the virus is subject to frequent mutations. To date, the sequence data from tens of thousands of virus isolates have revealed hundreds of mutations. Although most mutations have a minimum consequence, a small number of non-synonymous mutations may alter the virulence and antigenicity of the mutants. To evaluate the effects of viral mutations on drug safety and efficacy, we reviewed the biochemical features of the three main proteins and their potentials as drug targets, and analyzed the mutation profiles and their impacts on RNA therapeutics. We believe that monitoring and predicting mutation-introduced protein conformational changes in the three key viral proteins and evaluating their binding affinities and enzymatic activities with the U.S. Food and Drug Administration (FDA) regulated drugs by using computational modeling and machine learning processes can provide valuable information for the consideration of drug efficacy and drug safety for drug developers and drug reviewers. Finally, we propose an interactive database for drug developers and reviewers to use in evaluating the safety and efficacy of U.S. FDA regulated drugs with regard to viral mutations.


Subject(s)
COVID-19/drug therapy , COVID-19/genetics , Mutation/genetics , RNA/genetics , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Animals , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , COVID-19/metabolism , Drug Approval/methods , Drug Development/methods , Drug Development/trends , Humans , RNA/metabolism , RNA/therapeutic use , SARS-CoV-2/drug effects , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
12.
Drug Discov Today ; 26(10): 2439-2444, 2021 10.
Article in English | MEDLINE | ID: covidwho-1242920

ABSTRACT

In response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, a panel of assays has been developed and applied to screen collections of approved and investigational drugs for anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity in a quantitative high-throughput screening (qHTS) format. In this review, we applied data-driven approaches to evaluate the ability of each assay to identify potential anti-SARS-CoV-2 leads. Multitarget assays were found to show advantages in terms of accuracy and efficiency over single-target assays, whereas target-specific assays were more suitable for investigating compound mechanisms of action. Moreover, strict filtering with counter screens might be more detrimental than beneficial in identifying true positives. Thus, developing novel HTS assays acting simultaneously against multiple targets in the SARS-CoV-2 life cycle will benefit anti-COVID-19 drug discovery.


Subject(s)
COVID-19/drug therapy , Drug Development/trends , High-Throughput Screening Assays/trends , Antiviral Agents/pharmacology , Drug Discovery , Humans , Pandemics , SARS-CoV-2
13.
Drug Discov Today ; 26(6): 1337-1339, 2021 06.
Article in English | MEDLINE | ID: covidwho-1209943

ABSTRACT

Oncology is the frontline of drug development. The current pharmaceutical pipeline is disproportional focused on oncology, where about 1/3 of all phases of development is in this therapeutic area. The emphasis brings about substantial breakthroughs and has made positive impact on the quality of life. However, oncology remains a threat to human existence. To facilitate this process, a comprehensive list of novel/first molecularly targeted oncology drug approvals by the FDA from 2017 to 2020 is assessed. Here, we focus on molecularly targeted oncology drugs and not cytotoxic ones, although the latter remain important. To achieve this purpose, besides their sponsors, years of approval, drug classes, and cancer indications, clinical significance is included. The results show that approved molecularly targeted drugs span across diverse classes, including small molecule receptor inhibitors, and biologics such as monoclonal antibodies, antibody-drug conjugates, check-point inhibitors (i.e., PD1, PDL1, CTLA4) and CAR-T cell therapies. Although complete cure of cancer remains limited, we have made substantial inroads and more is yet to come. Moreover, many of these new knowledge can be extrapolated to other therapeutic areas, especially to those of currently unmet medical needs such as in neurology and other chronic diseases.


Subject(s)
Antineoplastic Agents, Immunological/pharmacology , COVID-19/epidemiology , Drug Development , Immune Checkpoint Inhibitors/pharmacology , Immunoconjugates/pharmacology , Medical Oncology , Neoplasms/drug therapy , Antineoplastic Agents/pharmacology , Drug Approval , Drug Development/organization & administration , Drug Development/trends , Humans , Medical Oncology/methods , Medical Oncology/trends , Molecular Targeted Therapy/methods , SARS-CoV-2 , United States
14.
Front Immunol ; 12: 669339, 2021.
Article in English | MEDLINE | ID: covidwho-1207698

ABSTRACT

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/standards , COVID-19/prevention & control , SARS-CoV-2/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/classification , Drug Development/standards , Drug Development/trends , Drug Evaluation/standards , Humans , Immunization/trends , Immunogenicity, Vaccine , Reference Standards , SARS-CoV-2/genetics
15.
Pharmacology ; 106(5-6): 244-253, 2021.
Article in English | MEDLINE | ID: covidwho-1206096

ABSTRACT

INTRODUCTION: The SARS-CoV-2 pandemic has led to one of the most critical and boundless waves of publications in the history of modern science. The necessity to find and pursue relevant information and quantify its quality is broadly acknowledged. Modern information retrieval techniques combined with artificial intelligence (AI) appear as one of the key strategies for COVID-19 living evidence management. Nevertheless, most AI projects that retrieve COVID-19 literature still require manual tasks. METHODS: In this context, we pre-sent a novel, automated search platform, called Risklick AI, which aims to automatically gather COVID-19 scientific evidence and enables scientists, policy makers, and healthcare professionals to find the most relevant information tailored to their question of interest in real time. RESULTS: Here, we compare the capacity of Risklick AI to find COVID-19-related clinical trials and scientific publications in comparison with clinicaltrials.gov and PubMed in the field of pharmacology and clinical intervention. DISCUSSION: The results demonstrate that Risklick AI is able to find COVID-19 references more effectively, both in terms of precision and recall, compared to the baseline platforms. Hence, Risklick AI could become a useful alternative assistant to scientists fighting the COVID-19 pandemic.


Subject(s)
Artificial Intelligence/trends , COVID-19/therapy , Data Interpretation, Statistical , Drug Development/trends , Evidence-Based Medicine/trends , Pharmacology/trends , Artificial Intelligence/statistics & numerical data , COVID-19/diagnosis , COVID-19/epidemiology , Clinical Trials as Topic/statistics & numerical data , Drug Development/statistics & numerical data , Evidence-Based Medicine/statistics & numerical data , Humans , Pharmacology/statistics & numerical data , Registries
16.
Nihon Saikingaku Zasshi ; 76(1): 3, 2021.
Article in Japanese | MEDLINE | ID: covidwho-1192526
19.
Biochem Pharmacol ; 188: 114543, 2021 06.
Article in English | MEDLINE | ID: covidwho-1163393

ABSTRACT

INTRODUCTION: There is an urgent need for new animal models of SARS CoV-2 infection to improve research and drug development. This brief commentary examines the deficits of current models and proposes several improved alternates. The existing single transgene mouse models poorly mimic the clinical features of COVID-19; those strains get a milder disease than human COVID-19 disease. Many of the current transgenic models utilize random integration of several copies of single ACE2 transgenes, resulting in unnatural gene expression and exhibit rapid lethality. We suggest preparing precision knock-in of selected human mini genes at the mouse initiation codon and knock-out of the mouse homolog as a better option. Three genes critical for infection are suggested targets, ACE2 (the viral cellular receptor), its co-infection protease TMRPSS2, and the primary antibody clearance receptor FcγRT. To offer the best platform for COVID 19 research, preparation of single, double, and triple humanized combinations offers the researcher the opportunity to better understand the contributions of these receptors, coreceptors to therapeutic efficacy. In addition, we propose to create the humanized strains in the C57BL/6J and BALB/c backgrounds. These two backgrounds are Th1 responders and Th2 responders, respectively, and allow modeling of the variability seen in human pathology including lung pathology and late sequelae of COVID-19 disease (BALB/c). We suggest the need to do a thorough characterization of both the short-term and long-term effects of SAR-CoV-2 infection at the clinical, virologic, histopathologic, hematologic, and immunologic levels. We expect the multiply humanized strains will be superior to the single-gene and multiple-gene-copy transgenic models available to date. These mouse models will represent state-of-the-art tools for investigating mechanisms of COVID-19 pathogenesis and immunity and developing vaccines and drugs.


Subject(s)
Biomedical Research/trends , COVID-19/drug therapy , COVID-19/genetics , Disease Models, Animal , SARS-CoV-2/drug effects , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/immunology , Animals , Animals, Genetically Modified , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/immunology , COVID-19 Vaccines/pharmacology , COVID-19 Vaccines/therapeutic use , Drug Development/trends , Humans , Mice , SARS-CoV-2/immunology
20.
Biosci Trends ; 15(2): 126-128, 2021 May 11.
Article in English | MEDLINE | ID: covidwho-1140772

ABSTRACT

Despite strict control measures implemented worldwide, the COVID-19 pandemic continues to rage. Several drugs, including lopinavir/ritonavir, hydroxychloroquine, dexamethasone, and remdesivir, have been evaluated for the treatment of COVID-19 during the past year. While most of the drugs failed to display efficacy in treating COVID-19, scientists have encouraged herd immunity to control the pandemic. Immunity generated after natural infection with SARS-CoV-2 is precarious, as indicated by real-world evidence in the form of epidemiological data from Manaus, Brazil. Vaccines using different platforms are therefore the most promising approach to help us return to normality. Although several vaccines have been authorized for emergency use, there are still many concerns regarding their accessibility, the vaccination rate, and most importantly, their efficacy in preventing infection with emerging virus variants. Continued virus surveillance and rapid redesign of new vaccines to counter new variants are crucial to fighting COVID-19. Rapid production and extensive vaccination are also essential to preventing the emergence of new variants. Nevertheless, antivirals including monoclonal antibodies and oral medicines need to be developed in light of uncertainties with regard to vaccination. In the battle between humans and SARS-CoV-2, the speed with which we fight the virus, and especially its emerging variants, is the key to winning.


Subject(s)
COVID-19 Vaccines , COVID-19/drug therapy , COVID-19/therapy , Pandemics , SARS-CoV-2 , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/isolation & purification , COVID-19 Vaccines/pharmacology , Drug Development/trends , Drug Resistance, Viral , Humans , Immunity, Herd , Immunization, Passive/trends , Pandemics/prevention & control , SARS-CoV-2/immunology
SELECTION OF CITATIONS
SEARCH DETAIL