Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path

Bram, Yaron; Duan, Xiaohua; Nilsson-Payant, Benjamin E.; Chandar, Vasuretha; Hao, Wu; Shore, Derek M.; Fajardo, Álvaro; Sinha, Saloni; Hassan, Nazmul; Weinstein, Harel; tenOever, Benjamin R.; Chen, Shuibing; Schwartz, Robert E.

doi:10.1021/acsbiomedchemau.2c00034

Cited by 3 publications

(1 citation statement)

References 85 publications

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“…Seeing the pattern of terrorist threats in Indonesia that choose targets in places that are considered strategic, through bombings on several churches on Christmas Eve in Medan, Pekanbaru, Jakarta, Mojokerto, Mataram, and others (Sarwono, 2012). The next terrorist also chose the target of the bombing at the Cirebon City Police mosque, and several police stations such as in Solo Police Station, Surabaya Police Station, Kartasura Police Post, Medan Police Station (Bram et al, 2022). Not only that, acts of terrorism have also occurred in Mako Brimob Kelapa Dua Depok in 2018, which was carried out by terrorism convicts, which at that time occurred in the detention room in the form of arresting 5 members of the Police Brimob until they died.…”

Section: Introductionmentioning

confidence: 99%

The Evolution of Mako Brimob Kelapa Dua Depok Strategy in Security Ahead of the 2024 Elections from the Threat of Terrorism

Saputra,

Priyanto

2024

ajosh

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Indonesia is a democratic country where general elections serve as a fundamental pillar in realizing democratic principles and act as a crucial mechanism ensuring active citizen participation in determining their representatives. Given the significance of the election moment as a pivotal point in Indonesia's political dynamics, it brings about a vulnerable risk of security disturbances, including terrorism threats. Indonesia bears a significant presence of terrorism, ranking third in the Asia-Pacific region according to the Global Terrorism Index 2023. The aim of this research is to elucidate the evolution of security strategies implemented by Mako Brimob Kelapa Dua Depok in facing terrorism threats related to the 2024 elections. The research method employed is qualitative, utilizing theories of security intelligence, social construction, and terrorism concepts. The results indicate that the 2024 General Election in Indonesia is a crucial political event, with a primary focus on anticipating terrorism threats due to the perceived intense political dynamics, increased political polarization, fierce competition among political parties, and extensive use of social media. Forms of terrorism leading up to the election include physical attacks, cyber-attacks, voter intimidation, and potential political conflicts. Security intelligence strategies in facing terrorism have evolved to involve prevention, intervention, and recovery. Strategic steps include establishing specialized intelligence agencies, technological advancements, and inter-agency collaboration. The evolution of security strategies related to the 2024 elections encompasses increased intelligence activities, enhanced intervention capabilities, and preparation for post-terrorism recovery. Special task forces, specialized equipment procurement, and collaboration with various stakeholders demonstrate Mako Brimob's efforts to enhance responses to terrorism threats

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Section: Introductionmentioning

confidence: 99%

The Evolution of Mako Brimob Kelapa Dua Depok Strategy in Security Ahead of the 2024 Elections from the Threat of Terrorism

Saputra,

Priyanto

2024

ajosh

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Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro

Mousavi

Zeynizadeh

Rimaz

2023

Bioorganic Chemistry

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The Conformational Space of the SARS-CoV-2 Main Protease Active Site Loops is Determined by Ligand Binding and Interprotomer Allostery

Lee,

Rauscher

2024

Preprint

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The main protease (Mpro) of SARS-CoV-2 is essential for viral replication and is, therefore, an important drug target. Here, we investigate two flexible loops in Mprothat play a role in catalysis. Using all-atom molecular dynamics simulations, we analyze the structural ensemble of Mproin an apo state and substrate-bound state. We find that the flexible loops can adopt open, intermediate (partly open) and closed conformations in solution, which differs from the partially closed state observed in crystal structures of Mpro. When the loops are in closed or intermediate states, the catalytic residues are more likely to be in close proximity, which is crucial for catalysis. Additionally, we find that substrate binding to one protomer of the homodimer increases the fre-quency of intermediate states in the bound protomer, while also affecting the structural propensity of the apo protomer’s flexible loops. Using dynamic network analysis, we identify multiple allosteric pathways connecting the two active sites of the homodimer. Common to these pathways is an allosteric hotspot involving the N-terminus, a critical region that comprises part of the binding pocket. Taken together, the results of our simulation study provide detailed insight into the relationships between the flexible loops and substrate binding in a prime drug target for COVID-19.

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Dual-Reporter System for Real-Time Monitoring of SARS-CoV-2 Main Protease Activity in Live Cells Enables Identification of an Allosteric Inhibition Path

Cited by 3 publications

References 85 publications

The Evolution of Mako Brimob Kelapa Dua Depok Strategy in Security Ahead of the 2024 Elections from the Threat of Terrorism

The Evolution of Mako Brimob Kelapa Dua Depok Strategy in Security Ahead of the 2024 Elections from the Threat of Terrorism

Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro

The Conformational Space of the SARS-CoV-2 Main Protease Active Site Loops is Determined by Ligand Binding and Interprotomer Allostery

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