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Novel AIFM1 antagonists with potential broad-spectrum antiviral activity.

Background

Apoptosis‑inducing factor (AIFM1) is a mitochondrial membrane protein that plays a crucial role in caspase-independent cell death pathways. Upon mitochondrial damage, AIFM1 translocates from mitochondria to the nucleus, triggering chromatin condensation and large-scale DNA fragmentation. This mechanism becomes particularly detrimental during viral infections, where many viruses, including SARS-CoV-2 and other coronaviruses, specifically target mitochondria to promote host cell apoptosis.

Recent studies by our researchers have elucidated the key role of mitochondrial dysfunction in coronavirus infections. Comprehensive analysis revealed that SARS-CoV-2 viral proteins trigger rapid mitochondrial membrane permeabilization, leading to upregulation of AIFM1 expression coincident with increased apoptosis. This process contributes to diffuse alveolar damage, lung injury, and impaired oxygen‑sensing mechanisms. Viral-mediated mitochondrial dysfunction also suppresses hypoxic pulmonary vasoconstriction (HPV), a critical physiological response that optimizes oxygen delivery during lung injury. 

COVID-19 and other viral respiratory infections cause significant morbidity and mortality through mitochondriopathy-induced apoptosis and suppression of hypoxic pulmonary vasoconstriction (HPV). Current antiviral treatments have limited efficacy, with many becoming ineffectual due to viral mutations leading to resistance. Other limitations include clinical constraints such as treatment must be initiated soon after symptom onset, as well as the need for intravenous delivery. Furthermore, severe viral infections are driven largely by host cell responses, such as immune responses, that many existing antivirals don’t affect. Thus, there remains an urgent need for novel antiviral therapeutic approaches.

Technology Overview

This invention presents novel small-molecule AIFM1 antagonists identified by in silico screening and validated through in vitro and in vivo studies.

In Vitro Studies: AIFM1 inhibitors Reduce Apoptosis and Viral Load in Infected Cells.

 shows data from AIF inhibitors applied to HCoV-OC43-infected human bronchial epithelial cells (BEAS-2B), demonstrating significant protection by AIFM1-inhibition:

• (i) Cell viability was preserved (note increased cell counts relative to vehicle);
• (ii) Apoptosis was significantly reduced (decreased TUNEL-positive cells), and
• (iii) Viral load was diminished compared to vehicle-treated controls. Note: Drpitor 1A is a novel drp1 inhibitor that prevents mitochondrial fission. For further information, see the technology ‘’&�Բ�����;

In Vivo Studies: AIFM1 Inhibitors Successfully Protect Lungs and Lung Function After Coronavirus Infection.

In , a murine model of MHV-1 mediated pneumonia (infected by intranasal inoculation of either MHV-1 (5000 PFU/17 μL)), shows significant benefits by AIF inhibitor treatment (1mg/kg, QD, IP) after infection:

• (i) Reduced lung edema and structural damage 
• (ii) micro-CT imaging shows improved lung perfusion of the same lungs in Figure 2(i) from AIFM1 inhibitor treatment 
• (iii) Hemodynamics of right ventricular systolic pressure (RVSP). Treatment with AIFM1 inhibitor restored HPV, as indicated by increased RVSP. Mice (vehicle and AIFM1 inhibitor treated) were provided with room air for ten minutes (Nx1; where Nx = normoxia), then hypoxic air (10% O,; Hx1, where Hx = hypoxia) for ten minutes and then animals were provided with room air again for ten minutes (Nx2).

Further Details:

• Archer, S. L., et al. (2022). SARS-CoV-2 mitochondriopathy in COVID-19 pneumonia exacerbates hypoxemia. Redox biology, _58_, 102508. 

Benefits

• Novel mechanism of action: To the research teams’ knowledge, these are the first small molecule inhibitors of AIFM1, representing a unique molecular mechanism for drug development 
• Broad anti-coronaviral activity and potential broad general antiviral activity due to the central role of mitochondria in viral infections
• Preserves mitochondrial health and other mitochondrial functions, such as oxygen sensing
• Reduced chance of viral resistance: host-targeted therapy reduces the likelihood of resistance development
• Treating Later Stage ARDS / COVID: restoration of HPV could benefit later-stage COVID patients, where currently available antiviral and monoclonal antibody drugs have limited benefit 

Applications

Primary Applications:

• Antiviral therapeutics for respiratory infections
• COVID-19 and long COVID treatment
• Emergency medicine for viral pneumonia
• Cardioprotection during cardiac procedures and arrests

Secondary Applications:

• Neuroprotection in stroke and neurodegenerative diseases
• Treatment of cardiomyopathies and heart failure
• Hepatoprotection in fatty liver diseases
• Research tools for mitochondrial biology studies

Opportunity

���ϳԹ���Դ is open to considering a number of commercialization mechanisms, including research collaborations, out-licensing, and venture funding to create a mitochondrial-target focused startup based upon AIFM1 and drp1 inhibitor development.

Licensing Opportunities:

• Exclusive licensing for pharmaceutical development
• Research collaborations for development of AIF inhibitors, including new indications
• Venture Funding

Patents

• US Patent Application US2025/0228853A1 “Apoptosis Inhibitors” (Published July 17, 2025)
• Canadian Patent Application “Apoptosis Inhibitors” filed January 16, 2025 (Application No. 19/024,516)

IP Status

Patent applications submitted

Seeking

• Licensing
• Seeking investment
• Development partner

Posted

November 20, 2025