Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition

Ebola virus (EBOV) is a non-segmented negative-sense RNA virus that causes a severe human disease. The ongoing EBOV outbreak in the Eastern part of Democratic Republic of the Congo has resulted to date in over 2500 confirmed cases including over 1500 deaths. Difficulties with vaccine administration indicate the necessity for development of new general drugs and therapeutic strategies against EBOV. Host Ser/Thr protein phosphatases, particularly PP1 and PP2A, facilitate EBOV transcription by dephosphorylating the EBOV VP30 protein and switching activity of the polymerase complex toward replication. Previously, we developed small molecule 1E7-03 that targeted host protein phosphatase-1 (PP1) and induces phosphorylation of EBOV VP30 protein thus shifting transcription–replication balance and inhibiting EBOV replication. Here, we developed a new EBOV inhibitor, 1E7-07, that potently inhibits EBOV replication and displays significantly improved metabolic stability when compared to previously described 1E7-03. Proteome analysis of VP30 shows that 1E7-07 increases its phosphorylation on Thr-119 and Ser-124 over 3-fold with p
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research

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Nature, Published online: 21 October 2019; doi:10.1038/d41586-019-03197-wThe World Health Organization says that the rate of new infections in the Democratic Republic of the Congo has dropped, as a vaccine moves closer to approval.
Source: Nature AOP - Category: Research Authors: Source Type: research
New cases are down to 15 a week from a high of 128 in April, but outbreaks are still popping up in remote and dangerous mining areas.
Source: NYT Health - Category: Consumer Health News Authors: Tags: Ebola Virus Epidemics Disasters and Emergencies Vaccination and Immunization World Health Organization Tedros Adhanom Ghebreyesus Congo, Democratic Republic of (Congo-Kinshasa) Uganda Source Type: news
[Vanguard] Health authorities in the Democratic Republic of Congo will introduce a Johnson&Johnson Ebola vaccine in November in the country's eastern provinces, to counter the current outbreak, they said.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
[Deutsche Welle] Many in the Democratic Republic of Congo have been waiting for this moment: A new vaccine to battle the Ebola outbreak is about to be released. The vaccine could reach broader parts of the population than before.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
CONCLUSIONS: Despite the unique nature of the 2014-2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials. Clinical trial registry number: This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193. PMID: 31623917 [PubMed - as supplied by publisher]
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Health authorities in Democratic Republic of Congo will introduce a Johnson&Johnson Ebola vaccine in November in the country's eastern provinces, to counter the current outbreak, they said.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
[New Times] Rwanda is planning a big vaccination campaign against the Ebola Virus Disease (EBV) for adults, adolescents, and children aged two years living within the vicinity of a possible Ebola outbreak.
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
(DAKAR, Senegal) — More than 4,000 people have died in Congo this year in the world’s largest measles outbreak, the United Nations children’s agency said Wednesday. The Central African nation is also battling an Ebola outbreak that has killed about half that number since August 2018. Since January, more than 200,000 cases of measles have been reported across Congo, UNICEF said. More than 140,000 involve children under 5, who also make up nearly 90 percent of deaths. “We’re facing this alarming situation because millions of Congolese children miss out on routine immunization and lack access to ...
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized Disease onetime the Democratic Republic of Congo Source Type: news
[MSF] Esther only winces slightly when a doctor on Doctors Without Borders/M édecins Sans Frontières' (MSF) vaccination team injects the Ebola vaccine called rVSV-ZEBOV into her left upper arm in Kimbangu, a community in the southwest of Beni--one of the recurring hotspots of the current Ebola epidemic in North Kivu province of the Democratic Republic of Congo (DRC). Justi n*, her two-and-a-half year-old son, bursts into tears when he sees a new syringe being filled, and only calms down a few minutes
Source: AllAfrica News: Health and Medicine - Category: African Health Source Type: news
The World Health Organization is "rationing" Ebola vaccines in Democratic Republic of Congo, with access controls meaning too few people at risk are being protected in an outbreak of the deadly disease, the aid group MSF said on Monday.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
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