國立高雄大學圖資館 |

Language: English

Back

Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus /Teena Bajaj.
Author:	Bajaj, Teena,
Description:	1 electronic resource (67 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
Notes:	Advisors: Murthy, Niren Committee members: Liu, Fenyong; Nomura, Daniel K.
Contained By:	Dissertations Abstracts International86-04B.
Subject:	Biochemistry.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31489097
ISBN:	9798384449171

Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus /
Bajaj, Teena,

Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus /Teena Bajaj. - 1 electronic resource (67 pages)

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

The emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (SCoV-2) caused catastrophic levels of morbidity in the world and presented the unmet need for treatments and drugs urgently. Small molecule therapeutics have tremendous potential to develop into antivirals and prevent the spread of infection. SCoV-2 genome encodes for 16 non-structural proteins (Nsps) that have been proven as potential target candidates. Two vital proteins, Papain-like protease (PLpro) (Papain-like protease, from Nsp3) and Non-structural protein 15 (Nsp15) were chosen as therapeutic targets to combat the SCoV-2 virus. PLpro is an essential protein that cleaves the polyprotein into its individual proteins to form a replication-transcription complex for viral replication and synthesis. On another hand, Nsp15 is a crucial protein that evades the host immune response by cleaving the viral RNA, therefore, Nsp15 inhibition stimulates the protective response. Both nsps are highly conserved proteins and the development of drugs against them could also act as an initial step for future coronavirus pandemics. To find the covalent inhibitors of PLpro and Nsp15, the electrophile library was screened against these two proteins using their respective fluorescent-based, high-throughput screening assay. To find the inhibitors against the PLpro, a chemical library was screened against the recombinantly purified PLpro using a fluorescent-based high throughput screening assay. One compound, based on mercaptopyrimidine inhibited PLpro invitro and SARS-CoV-2 viral replication in Vero E6 cells. This compound presented the first example of a thiol-targeted reversible covalent inhibitor of PLpro. In the case of Nsp15, an acrylamide-based electrophile library was screened to find cysteine-binding inhibitors. This discovered a new class of Nsp15 covalent inhibitors. This study not only discovered new covalent lead hits against crucial proteins from SCoV-2, but also a new platform to develop new potent drugs against coronaviruses for future pandemics.

English

ISBN: 9798384449171Subjects--Topical Terms:

188609
Biochemistry.
Subjects--Index Terms:

Papain-like protease

Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus /
LDR:03556nmm a22004093i 4500 001 676365
005 20250420214351.5
006 m o d
007 cr|nu||||||||
008 250901s2024 miu||||||m |||||||eng d
020 $a 9798384449171
035 $a (MiAaPQD)AAI31489097
035 $a AAI31489097
040 $a MiAaPQD $b eng $c MiAaPQD $e rda
100 1 $a Bajaj, Teena, $e author. $3 990167
245 1 0 $a Discovery of Small Molecule Drugs Against Crucial Proteins, Papain-Like Protease (PLpro) and Non-Structural Protein 15 (Nsp15), From SARS-CoV-2 Virus / $c Teena Bajaj.
264 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2024
300 $a 1 electronic resource (67 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
500 $a Advisors: Murthy, Niren Committee members: Liu, Fenyong; Nomura, Daniel K.
502 $b Ph.D. $c University of California, Berkeley $d 2024.
520 $a The emergence and rapid spread of the severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (SCoV-2) caused catastrophic levels of morbidity in the world and presented the unmet need for treatments and drugs urgently. Small molecule therapeutics have tremendous potential to develop into antivirals and prevent the spread of infection. SCoV-2 genome encodes for 16 non-structural proteins (Nsps) that have been proven as potential target candidates. Two vital proteins, Papain-like protease (PLpro) (Papain-like protease, from Nsp3) and Non-structural protein 15 (Nsp15) were chosen as therapeutic targets to combat the SCoV-2 virus. PLpro is an essential protein that cleaves the polyprotein into its individual proteins to form a replication-transcription complex for viral replication and synthesis. On another hand, Nsp15 is a crucial protein that evades the host immune response by cleaving the viral RNA, therefore, Nsp15 inhibition stimulates the protective response. Both nsps are highly conserved proteins and the development of drugs against them could also act as an initial step for future coronavirus pandemics. To find the covalent inhibitors of PLpro and Nsp15, the electrophile library was screened against these two proteins using their respective fluorescent-based, high-throughput screening assay. To find the inhibitors against the PLpro, a chemical library was screened against the recombinantly purified PLpro using a fluorescent-based high throughput screening assay. One compound, based on mercaptopyrimidine inhibited PLpro invitro and SARS-CoV-2 viral replication in Vero E6 cells. This compound presented the first example of a thiol-targeted reversible covalent inhibitor of PLpro. In the case of Nsp15, an acrylamide-based electrophile library was screened to find cysteine-binding inhibitors. This discovered a new class of Nsp15 covalent inhibitors. This study not only discovered new covalent lead hits against crucial proteins from SCoV-2, but also a new platform to develop new potent drugs against coronaviruses for future pandemics.
546 $a English
590 $a School code: 0028
650 4 $a Biochemistry. $3 188609
650 4 $a Cellular biology. $3 708607
650 4 $a Epidemiology. $3 191577
653 $a Papain-like protease
653 $a Mercaptopyrimidine
653 $a Covalent inhibitors
690 $a 0487
690 $a 0379
690 $a 0766
710 2 $a University of California, Berkeley. $b Comparative Biochemistry. $e degree granting institution. $3 990168
720 1 $a Murthy, Niren $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-04B.
790 $a 0028
791 $a Ph.D.
792 $a 2024
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31489097