VIGILANT

EU-funded research group VIGILANT: Broad-spectrum antivirals for future pandemics. Join us for updates & collabs! #HorizonEurope

[VIGILANT @VIGILANT_EU]

🚨VIGILANT is developing antivirals that block cellular factors viruses depend on - proteases and Sec61.

This thread 🧵 explains why cellular proteases are attractive targets to stop viruses before they spread. 🦠🔒

[VIGILANT @VIGILANT_EU]

VIGILANT seeks to develop inhibitors of virus-activating host cell proteases.

This study shows that N-glycans upstream of the furin cleavage site in SARS-CoV-2 Spike influence Spike processing.

A reminder that the cleavage motif isn't the whole story- the surrounding structural and glycan environment matters too.

https://t.co/o4FQsx3PoS

[Stefan Pöhlmann @snpoehlm]

An exciting new preprint offers insights into how SARS-CoV-2 and other coronaviruses can acquire cleavage motifs for the cellular protease furin. A thread on the importance of the furin motif in the SARS-CoV-2 spike and its possible origins.🧵

To infect a cell, coronaviruses must first get inside. The spike protein handles this, with help from the host cell.

Spike binds receptors on the cell surface. After activation by cellular proteases, it drives fusion of the viral and cellular membranes, allowing delivery of the viral genome into the cell. This step is essential for infection.

For SARS-CoV-2, spike activation involves two key cleavages. Furin cleaves at the S1/S2 site during virus production. A second cleavage by TMPRSS2 at S2′ then occurs during entry into human respiratory cells.

The furin cleavage motif matters: disrupting it reduces infection of human respiratory cells and attenuates SARS-CoV-2 in animal models.

The closest known relatives of SARS-CoV-2 (sarbecoviruses) come from bats, consistent with an evolutionary ancestry in bat coronaviruses. Yet none of the known closely related bat sarbecoviruses has a furin cleavage motif at S1/S2. This absence has featured prominently in discussions of SARS-CoV-2’s origin, including claims that the site might have been acquired through laboratory manipulation.

Let’s examine whether furin cleavage motifs are generally advantageous for sarbecoviruses and how they can be acquired.

[Stefan Pöhlmann @snpoehlm]

Filoviruses are among the most lethal viruses known to infect humans. Yet despite decades of research, major questions about their ecology, evolution, host range, and potential for wider geographic spread remain unresolved.

➡️A thread on Ebola, Marburg, and related filoviruses.

[VIGILANT @VIGILANT_EU]

Repurposing clinical candidates against Nipah virus and Hendra virus

Cathepsin L inhibitors showed potent antiviral activity in cell culture, including the clinical-stage inhibitor relacatib.

Relacatib failed to protect Syrian hamsters against Nipah virus infection, likely due to rapid drug clearance and insufficient exposure.

The study underscores both the promise and the translational challenges of targeting cathepsin L as a broad-spectrum antiviral strategy.

ACS Infectious Diseases
https://t.co/CA4eHj9dlH

[VIGILANT @VIGILANT_EU]

Furin Inhibition Protects Against Acute Lung Injury in a Mouse Model of Pseudomonas Aeruginosa Infection https://t.co/1XrTEwFrAZ

[VIGILANT @VIGILANT_EU]

Furin as target for suppression of mosquito-borne viruses

➡️Furin encoding genes identified in mosquito cell lines.

➡️A furin inhibitor blocked Semliki Forest virus infection of mosquito cell lines.

Centurión et al. Virol J 11;23(1):92. 2026 Mar
https://t.co/XtivsuwRwQ

[VIGILANT @VIGILANT_EU]

https://t.co/SuQTlM3w9f

[VIGILANT @VIGILANT_EU]

Hantaviruses are rodent-borne pathogens that can cause severe disease in humans. Andes virus, found in South America, is the only hantavirus known to occasionally spread between people, typically after close contact.

The ongoing cruise ship-associated outbreak is a sobering reminder of the continuing threat posed by zoonotic viruses. We hope the outbreak can be swiftly contained and extend our thoughts to the affected families and communities.

There are currently no highly effective antivirals against hantaviruses, underscoring the importance of developing broad-spectrum antiviral strategies against zoonotic pathogens.

[World Health Organization (WHO) @WHO]

Swiss authorities have confirmed a case of #hantavirus identified in a passenger from the MV Hondius cruise ship.

He had responded to an email from the ship’s operator informing the passengers of the health event, and presented himself to a hospital in Zurich, Switzerland, and is receiving care.

In line with the International Health Regulations (IHR), WHO is working with relevant countries to support international contact tracing, to ensure that those potentially exposed are monitored and that any further disease spread is limited.

The type of virus in this outbreak has been confirmed as Andes hantavirus by the National Institute for Communicable Diseases @nicd_sa, South Africa and the Geneva University Hospitals @hug_ge, Switzerland
The support of the Institut Pasteur de Dakar @PasteurDakar, Senegal and the Administración Nacional de Laboratorios e Institutos de Salud @ANLIS_Malbran, Argentina has also been critical in responding to this event.

As of 6 May, there are 8 cases, 3 of whom are confirmed as hantavirus by laboratory testing.

WHO will continue to work with countries to ensure that the patients, contacts, passengers and crew have the information and support they need to stay safe and prevent spread.

[VIGILANT @VIGILANT_EU]

Interesting study by Li and colleagues:

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease of pigs caused by a virus - PRRSV.

They report that the host protein SSR4 (Signal Sequence Receptor Subunit 4), a small membrane protein that forms part of the TRAP complex (translocon-associated protein complex), mediates PRRSV-induced endoplasmic reticulum stress via interaction with the viral protein Nsp2.

Interestingly, drugs that disrupted this hijacked ER stress pathway - especially ER stress inducers - showed potent antiviral activity.

These findings highlight proteins associated with the ER translocon - a key target of @VIGILANT_EU - as promising targets for antiviral intervention.

Journal of Virology
https://t.co/mSLlVNF7YB

[Journal of Clinical Investigation @jclinicalinvest]

Platelet hyperactivity in type 2 diabetes increases the risk for blood clots.

Freda H. Passam & team @Sydney_Uni now identify SEC61 as an ER calcium leak channel in platelets—upregulation of which contributes to platelet hyperreactivity in diabetes:
https://t.co/2jcvXky1DM

Check out the effect of the SEC61 inhibitor anisomycin on platelet adhesion.

[Solomon T Zeleke @ztsolomon]

Targeting the gate: The rise of Sec61 inhibitors in cancer therapy https://t.co/OlaNuvjzgX

[inmunoes @inmunoes]

SEC61: a potential therapeutic target in transplantation https://t.co/yYu9rKCLxL #FrontImmunol

[VIGILANT @VIGILANT_EU]

VIGILANT annual meeting in Ljubljana 🇸🇮

New findings, great discussions, and valuable input from our Scientific Advisory Board. Projects are advancing, collaborations strengthening, and progress toward broad-spectrum antivirals continues to advance.

Thanks to all involved - and to the European Union for funding!

[VIGILANT @VIGILANT_EU]

Just over three weeks until our annual meeting, with talks by renowned experts open to the public.

The talks will be available in person and online on the day. Virologists in Ljubljana, be sure to drop by!

We are looking forward to sharing our knowledge with you!

[VIGILANT @VIGILANT_EU]

Structures of Marburgvirus glycoprotein and its complex with NPC1 receptor | Nature https://t.co/vXBzf3jSFM

[VIGILANT @VIGILANT_EU]

VIGILANT will be holding its 2026 Annual Meeting in Ljubljana in April. Our keynote speeches are open to the public across two sessions on the Friday. We are looking forward to seeing members virology community in Slovenia in full force!

[VIGILANT @VIGILANT_EU]

Structural insights into the RNA-dependent RNA polymerase complexes from highly pathogenic Marburg and Ebola viruses

https://t.co/uAbFi294pY

[VIGILANT @VIGILANT_EU]

Structural basis of Nipah virus RNA synthesis

https://t.co/9WeKzNWXl9

[VIGILANT @VIGILANT_EU]

A much-needed vaccine for Nipah virus https://t.co/uADRfnu4kI

[VIGILANT @VIGILANT_EU]

The 2024 outbreak of undiagnosed febrile illness in Panzi, Democratic Republic of the Congo, was mainly due to malaria and respiratory virus infections - not an emerging pathogen.

https://t.co/5sTLz1VM6c