A Comparative High-Throughput Screening Protocol to Identify Entry Inhibitors of Enveloped Viruses

Emerging and reemerging human viral pathogens pose great public health concerns since therapeutics against these viruses are limited. Thus, there is an urgent need to develop novel drugs that can block infection of either a specific virus or a number of viruses. Viral entry is thought to be an ideal target for potential therapeutic prevention. One of the challenges of developing antivirals is that most of these viruses are highly pathogenic and therefore require high biosafety-level containment. In this study, we have adopted a comparative high-throughput screening protocol to identify entry inhibitors for three enveloped viruses (Marburg virus, influenza virus H5N1, and Lassa virus) using a human immunodeficiency virus–based pseudotyping platform. We demonstrate the utility of this approach by screening a small compound library and identifying putative entry inhibitors for these viruses. One major advantage of this protocol is to reduce the number of false positives in hit selection, and we believe that the protocol is useful for inhibitor screening for many enveloped viruses.

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High-Throughput Screening of Viral Entry Inhibitors Using Pseudotyped Virus

Current Protocols in Pharmacology ◽

10.1002/0471141755.ph13b03s51 ◽

2010 ◽

pp. 13B.3.1-13B.3.17 ◽

Cited By ~ 4

Author(s):

Arnab Basu ◽

Debra M. Mills ◽

Terry L. Bowlin

Keyword(s):

High Throughput ◽

Viral Entry ◽

High Throughput Screening ◽

Pseudotyped Virus ◽

Entry Inhibitors

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Development of a Cell-Based Assay for Identification of Viral Entry Inhibitors Against SARS-CoV by High Throughput Screening (HTS)

Antiviral Research ◽

10.1016/j.antiviral.2007.01.143 ◽

2007 ◽

Vol 74 (3) ◽

pp. A82-A82

Author(s):

C ZHANG ◽

Y FENG ◽

G WONG ◽

L WANG ◽

J CECHETTO ◽

...

Keyword(s):

High Throughput ◽

Viral Entry ◽

High Throughput Screening ◽

Entry Inhibitors ◽

A Cell

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High-Throughput Screening—Based Identification of Paramyxovirus Inhibitors

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057108321089 ◽

2008 ◽

Vol 13 (7) ◽

pp. 591-608 ◽

Cited By ~ 13

Author(s):

Jeong-Joong Yoon ◽

Dhruv Chawla ◽

Tanja Paal ◽

Maina Ndungu ◽

Yuhong Du ◽

...

Keyword(s):

High Throughput ◽

Viral Entry ◽

High Throughput Screening ◽

Measles Virus ◽

Human Pathogens ◽

Response Curves ◽

Major Morbidity ◽

Screening Protocol ◽

Hit Identification ◽

Chemistry Journal

Several members of the paramyxovirus family constitute major human pathogens that, collectively, are responsible for major morbidity and mortality worldwide. In an effort to develop novel therapeutics against measles virus (MV), a prominent member of the paramyxovirus family, the authors report a high-throughput screening protocol that uses a nonrecombinant primary MV strain as targets. Implementation of the assay has yielded 60 hit candidates from a 137,500-entry library. Counterscreening and generation of dose-response curves narrows this pool to 35 compounds with active concentrations ≤15.3 µM against the MV-Alaska strain and specificity indices ranging from 36 to >500. Library mining for structural analogs of several confirmed hits combined with retesting of identified candidates reveals a high accuracy of primary hit identification. Eleven of the confirmed hits interfere with viral entry, whereas the remaining 24 compounds target postentry steps of the viral life cycle. Activity testing against selected members of the paramyxovirus family reveals 3 patterns of activity: 1) exclusively MV-specific blockers, 2) inhibitors of MV and related viruses of the same genus, and 3) broader range inhibitors with activity against a different Paramyxovirinae genus. Representatives of the last class may open avenues for the development of broad-range paramyxovirus inhibitors through hit-to-lead chemistry. ( Journal of Biomolecular Screening 2008:591-608)

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High-throughput computational-experimental screening protocol for the discovery of bimetallic catalysts

npj Computational Materials ◽

10.1038/s41524-021-00605-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Byung Chul Yeo ◽

Hyunji Nam ◽

Hyobin Nam ◽

Min-Cheol Kim ◽

Hong Woo Lee ◽

...

Keyword(s):

High Throughput ◽

Bimetallic Catalysts ◽

High Throughput Screening ◽

Direct Synthesis ◽

Catalytic Performance ◽

Platinum Group Metals ◽

Pt Catalyst ◽

Electronic Density ◽

Bimetallic Alloy ◽

Screening Protocol

AbstractTo accelerate the discovery of materials through computations and experiments, a well-established protocol closely bridging these methods is required. We introduce a high-throughput screening protocol for the discovery of bimetallic catalysts that replace palladium (Pd), where the similarities in the electronic density of states patterns were employed as a screening descriptor. Using first-principles calculations, we screened 4350 bimetallic alloy structures and proposed eight candidates expected to have catalytic performance comparable to that of Pd. Our experiments demonstrate that four bimetallic catalysts indeed exhibit catalytic properties comparable to those of Pd. Moreover, we discover a bimetallic (Ni-Pt) catalyst that has not yet been reported for H2O2 direct synthesis. In particular, Ni61Pt39 outperforms the prototypical Pd catalyst for the chemical reaction and exhibits a 9.5-fold enhancement in cost-normalized productivity. This protocol provides an opportunity for the catalyst discovery for the replacement or reduction in the use of the platinum-group metals.

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