scholarly journals Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons Between Candidate Anti-Coronavirus Compounds

2020 ◽  
Author(s):  
Philip L Tzou ◽  
Kaiming Tao ◽  
Janin Nouhin ◽  
Soo-Yon Rhee ◽  
Benjamin D Hu ◽  
...  
Keyword(s):  
Animal Model ◽  
Protease Inhibitors ◽  
Clinical Studies ◽  
Research Database ◽  
Endosomal Trafficking ◽  
Model Studies ◽  
Antiviral Compounds ◽  
The Us ◽  
Entry Assay

Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of July 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained >2,400 cell culture, entry assay and biochemical experiments, 240 animal model studies, and 56 clinical studies from >300 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for approximately 85% of the data. Approximately 75% of experiments involved compounds with a known or likely mechanism of action, including receptor binding inhibitors and monoclonal antibodies (20%); viral protease inhibitors (18%); polymerase inhibitors (9%); interferons (8%); fusion inhibitors (8%); host endosomal trafficking inhibitors (7%); and host protease inhibitors (5%). For 724 compounds with a known or likely mechanism, 95 (13%) are licensed in the US for other indications, 72 (10%) are licensed outside the US or are in human trials, and 557 (77%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.

scholarly journals Coronavirus Antiviral Research Database (CoV-RDB): An Online Database Designed to Facilitate Comparisons between Candidate Anti-Coronavirus Compounds

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1006
Author(s):  
Philip L. Tzou ◽  
Kaiming Tao ◽  
Janin Nouhin ◽  
Soo-Yon Rhee ◽  
Benjamin D. Hu ◽  
...  
Keyword(s):  
Animal Model ◽  
Protease Inhibitors ◽  
Clinical Studies ◽  
Research Database ◽  
Model Studies ◽  
Fusion Inhibitors ◽  
Antiviral Compounds ◽  
Entry Assay ◽  
The U.S

Background: To prioritize the development of antiviral compounds, it is necessary to compare their relative preclinical activity and clinical efficacy. Methods: We reviewed in vitro, animal model, and clinical studies of candidate anti-coronavirus compounds and placed extracted data in an online relational database. Results: As of August 2020, the Coronavirus Antiviral Research Database (CoV-RDB; covdb.stanford.edu) contained over 2800 cell culture, entry assay, and biochemical experiments, 259 animal model studies, and 73 clinical studies from over 400 published papers. SARS-CoV-2, SARS-CoV, and MERS-CoV account for 85% of the data. Approximately 75% of experiments involved compounds with known or likely mechanisms of action, including monoclonal antibodies and receptor binding inhibitors (21%), viral protease inhibitors (17%), miscellaneous host-acting inhibitors (10%), polymerase inhibitors (9%), interferons (7%), fusion inhibitors (5%), and host protease inhibitors (5%). Of 975 compounds with known or likely mechanism, 135 (14%) are licensed in the U.S. for other indications, 197 (20%) are licensed outside the U.S. or are in human trials, and 595 (61%) are pre-clinical investigational compounds. Conclusion: CoV-RDB facilitates comparisons between different candidate antiviral compounds, thereby helping scientists, clinical investigators, public health officials, and funding agencies prioritize the most promising compounds and repurposed drugs for further development.

“In vitro” and in Animal Model Studies on a Double Virus- Inactivated Factor VIII Concentrate

1995 ◽  
Vol 74 (03) ◽  
pp. 868-873 ◽  
Author(s):  
Silvana Arrighi ◽  
Roberta Rossi ◽  
Maria Giuseppina Borri ◽  
Vladimir Lesnikov ◽  
Marina Lesnikov ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Animal Model ◽  
Factor Viii ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Virus Inactivation ◽  
Enveloped Viruses ◽  
Model Studies ◽  
Heat Treated

SummaryTo improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100° C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (SID) method during the manufacturing process.The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.

Curcumin-gold-polyethylene glycol nanoparticles as a nanosensitizer for photothermal and sonodynamic therapies: In vitro and animal model studies

2021 ◽  
Vol 33 ◽  
pp. 102139
Author(s):  
Z. Kayani ◽  
R. Dehdari Vais ◽  
E. Soratijahromi ◽  
S. Mohammadi ◽  
N. Sattarahmady
Keyword(s):  
Animal Model ◽  
Polyethylene Glycol ◽  
Model Studies

scholarly journals Engineered nanoparticle bio-conjugates toxicity screening: The xCELLigence cells viability impact

Bioimpacts ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 195-203
Author(s):  
Clarence S Yah ◽  
Geoffrey S. Simate
Keyword(s):  
Animal Model ◽  
Real Time ◽  
In Vitro Toxicity ◽  
Toxicity Screening ◽  
Limited Information ◽  
Size Estimation ◽  
Model Studies ◽  
Engineered Nanoparticle

Introduction: The vast diverse products and applications of engineered nanoparticle bio-conjugates (ENPBCs) are increasing, and thus flooding the-markets. However, the data to support risk estimates of ENPBC are limited. While it is important to assess the potential benefits, acceptability and uptake, it is equally important to understand where ENPBCs safety is and how to expand and affirm consumer security concerns. Methods: Online articles were extracted from 2013 to 2016 that pragmatically used xCELLigence real-time cell analysis (RTCA) technology to describe the in-vitro toxicity of ENPBCs. The xCELLigence is a +noninvasive in vitro toxicity monitoring process that mimics exact continuous cellular bio-responses in real-time settings. On the other hand, articles were also extracted from 2008 to 2016 describing the in vivo animal models toxicity of ENPBCs with regards to safety outcomes. Results: Out of 32 of the 121 (26.4%) articles identified from the literature, 23 (71.9%) met the in-vitro xCELLigence and 9(28.1%) complied with the in vivo animal model toxicity inclusion criteria. Of the 23 articles, 4 of them (17.4%) had no size estimation of ENPBCs. The xCELLigence technology provided information on cell interactions, viability, and proliferation process. Eighty-three (19/23) of the in vitro xCELLigence technology studies described ENPBCs as nontoxic or partially nontoxic materials. The in vivo animal model provided further toxicity information where 1(1/9) of the in vivo animal model studies indicated potential animal toxicity while the remaining results recommended ENPPCs as potential candidates for drug therapy though with limited information on toxicity. Conclusion: The results showed that the bioimpacts of ENPBCs either at the in vitro or at in vivo animal model levels are still limited due to insufficient information and data. To keep pace with ENPBCs biomedical products and applications, in vitro, in vivo assays, clinical trials and long-term impacts are needed to validate their usability and uptake. Besides, more real-time ENPBCs-cell impact analyses using xCELLigence are needed to provide significant data and information for further in vivo testing.

scholarly journals Potent protease inhibitors of deadly lagoviruses: rabbit hemorrhagic disease virus and European brown hare syndrome virus

2022 ◽  
Author(s):  
Krishani D Perera ◽  
David K Johnson ◽  
Scott Lovell ◽  
William Groutas ◽  
Kyeong-Ok Chang ◽  
...  
Keyword(s):  
Protease Inhibitors ◽  
Homology Modelling ◽  
Rabbit Hemorrhagic Disease Virus ◽  
Hemorrhagic Disease ◽  
Brown Hare ◽  
European Brown Hare ◽  
Rabbit Hemorrhagic Disease ◽  
The Us ◽  
European Brown Hare Syndrome

Rabbit hemorrhagic disease (RHD) and European brown hare syndrome (EBHS) are highly contagious diseases caused by lagoviruses in the Caliciviridae family and mainly affect rabbits and hares, respectively. These infectious diseases are associated with high mortality and a serious threat to domesticated (farmed and pet) and wild rabbits and hares, including endangered species such as Riparian brush rabbits. In the US, only isolated cases of RHD had been reported until Spring 2020. However, RHD caused by RHD type 2 virus (RHDV2) was unexpectedly reported in April 2020 in New Mexico and has subsequently spread to several US states infecting wild rabbits and hares. Since it is almost impossible to control and eradicate the virus from wild animals, it is highly likely RHD will become endemic in the US. Vaccines are available for RHD, however, there is no specific treatment for these deadly diseases. RHDV and EBHSV encode a 3C-like protease (3CLpro), which is essential for virus replication and a promising target for antiviral drug development. We have previously generated focused small molecule libraries of 3CLpro inhibitors and demonstrated the in vitro potency and in vivo efficacy of some protease inhibitors against viruses that encode 3CLpro including caliciviruses and coronaviruses. Here we established the enzyme assay and cell-based assays for these uncultivable viruses to determine the in vitro activity of 3CLpro inhibitors, including GC376, a protease inhibitor being developed for feline infectious peritonitis, and identified potent inhibitors of RHDV1 and 2 and EBHSV. In addition, structure-activity relationship study and homology modelling of the 3CLpros and inhibitors revealed that lagoviruses share similar structural requirements for 3CLpro inhibition with other caliciviruses.

scholarly journals Influence of Dietary Compounds on Arsenic Metabolism and Toxicity. Part I—Animal Model Studies

Toxics ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 258
Author(s):  
Monika Sijko ◽  
Lucyna Kozłowska
Keyword(s):  
Animal Model ◽  
Folic Acid ◽  
Animal Studies ◽  
Current Knowledge ◽  
Vitamin B2 ◽  
Laboratory Studies ◽  
Model Studies ◽  
Adverse Health Effects

Population and laboratory studies indicate that exposure to various forms of arsenic (As) is associated with many adverse health effects; therefore, methods are being sought out to reduce them. Numerous studies focus on the effects of nutrients on inorganic As (iAs) metabolism and toxicity, mainly in animal models. Therefore, the aim of this review was to analyze the influence of methionine, betaine, choline, folic acid, vitamin B2, B6, B12 and zinc on the efficiency of iAs metabolism and the reduction of the severity of the whole spectrum of disorders related to iAs exposure. In this review, which includes 58 (in vivo and in vitro studies) original papers, we present the current knowledge in the area. In vitro and in vivo animal studies showed that methionine, choline, folic acid, vitamin B2, B12 and zinc reduced the adverse effects of exposure to iAs in the gastrointestinal, urinary, lymphatic, circulatory, nervous, and reproductive systems. On the other hand, it was observed that these compounds (methionine, choline, folic acid, vitamin B2, B12 and zinc) may increase iAs metabolism and reduce toxicity, whereas their deficiency or excess may impair iAs metabolism and increase iAs toxicity. Promising results of in vivo and in vitro on animal model studies show the possibility of using these nutrients in populations particularly exposed to As.

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