[SRBase] BOINC Games sprint 07/15/2024 08:00 (UTC) - 07/18/2024 08:00 (UTC)

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View article · Mon, 15 Jul 2024 11:24:29 +0000

[SRBase] Trial Factoring 75-76bit range started

The next batch of 50k tests is uploading.

The runtime is now ~2h40min on a RX5500 XT and decreasing on higher ranges.

View article · Thu, 11 Jul 2024 10:02:09 +0000

[SIDock@home] Target # 23: Ebola GP1

Dear participants,

as target # 22 is almost finished, we are glad to introduce the next target. Most of you have voted for Ebolavirus glycoprotein (GP) (174 out of 425 votes, wow!)

The Ebola virus is a highly virulent pathogen responsible for causing Ebola hemorrhagic fever, a severe and often fatal disease. A key factor in the virus's ability to infect host cells and cause disease is its surface glycoprotein (GP), making it an attractive target for antiviral drug development. The Ebola GP is a trimeric protein composed of two subunits per monomer: GP1, responsible for receptor binding, and GP2, which mediates fusion between the viral and host cell membranes. Initially synthesized as a precursor protein, the GP is cleaved by host proteases (furin, cathepsin) into its functional subunits, a process essential for its role in mediating viral entry. The GP facilitates the virus's attachment to the host cell surface, followed by conformational changes that enable membrane fusion, allowing the virus to enter the host cell (to the host endosomal Niemann-Pick C1 (NPC1) receptor or via direct membrane binding; Vaknin et al.; ACS Infect. Dis. 2024, 10, 5, 1590–1601).

Targeting the GP for drug development is advantageous due to its essential role in viral infection, its highly conserved structure among different Ebola virus strains, and the availability of specific binding cavities that can accommodate small-molecule inhibitors. Structural studies using techniques such as X-ray crystallography have identified these binding cavities and elucidated the GP's conformation in both its free and inhibited states. These insights enable the design of drugs that can specifically bind to and inhibit the GP by stabilizing it in its pre-fusion conformation or interfering with its cleavage, thereby preventing the necessary conformational changes for membrane fusion. We will employ high-resolution structures to conduct virtual screening experiments coupled to molecular dynamics simulations to ultimately identify potential GP inhibitors/modulators.

Promising compounds identified through these computational methods will hopefully undergo further validation using biochemical assays, pseudovirus entry assays, and structural analyses to confirm their inhibitory activity. Targeting the GP offers specificity, as it minimizes off-target effects on host cells and reduces the likelihood of resistance development. Moreover, due to the conserved nature of the GP, drugs targeting it could be effective against multiple Ebola virus strains and variants.

We hope that our computations will contribute to the fight against Ebola!

View article · Thu, 11 Jul 2024 09:02:55 +0000

Computing power · Certificate · · Poll

• Create a BOINC project
  
• Run Autodock Vina jobs with BOINC Central and Raccoon2

Programmers:

• Visit the BOINC github repo

Windows malware reported
We have received several reports of malware that installs and runs the 8.0.2 BOINC client on Windows computers. We are investigating this; we currently don't know how the malware works or how to defeat it. We'll report whatever we learn here.

This is not a vulnerability in BOINC; rather, it's malware that illegally installs BOINC.
26 Jun 2024, 23:01:38 UTC · Discuss

User Manual moved to Github
As part of our effort to move documentation to Github, we have moved the User Manual from Mediawiki on the UCB server to Markdown on Github.
15 Jun 2024, 21:26:02 UTC · Discuss

BOINC client 8.0.2 released
The 8.0.2 version of the BOINC client has been released for all platforms. Download it here. Release notes are here.
30 May 2024, 11:07:49 UTC · Discuss

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