A PLATFORM FOR FIGHTING INFECTIOUS DISEASES
The S-MGB platform delivers molecules that can kill bacteria, fungi, parasites, and viruses by binding to multiple sites on DNA and RNA , disrupting the fundamental cellular functions of these critical nucleic acids. Importantly, the multiple modes of action (MOAs) of S-MGBs not only enables rapid killing of pathogens, but also provides resilience to the development of antimicrobial resistance (AMR).
Having completed essential chemical and biological profiling of the 2nd generation of S-MGB molecules, now is the time to accelerate the development process and rapidly evolve the lead compounds into disease-beating medicines. Rostra is focussed on a collaborative approach to developing S-MGBs, recently starting a research project supported by the CF AMR Syndicate to find molecules suitable for development into medicines to treat fungal lung infections in patients living with cystic fibrosis. This will build on earlier work done in the US with the NIH as part of NIAID's pre-clinical services development programme.
ANTI-FUNGAL
Serious fungal diseases can be life-threatening and are particularly prevalent in patients with compromised immune systems. The wide use of azole chemicals in agriculture has resulted in azole-resistant fungi. Azoles have been the first choice for treating serious human fungal infections but are now becoming less effective due to resistance. S-MGBs have activity against, for example:
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Drug (azole)-resistant pathogens including Aspergillus and Candida spp.
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Candida auris, added to the CDC ‘Urgent’ List in 2019
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Opportunistic pathogens such as Candida glabrata, where azole-resistance is now problematic
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Cryptococcus neoformans causing meningitis, particularly in immunocompromised patients, and now developing drug-resistance
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Emerging pathogens such as Scedosporium and Lomentospora spp.
The COVID pandemic has sharpened our appreciation of viral disease, its rapid spread and the consequences. Although initially developed as DNA targets, S-MGBs also bind to RNA. Hence they have activity against viruses. S-MGBs are even active against single-stranded RNA viruses, for example:
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SARS-CoV-2
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Hepatitis C (HCV)
ANTI-VIRAL
ANTI-PARASITIC​
Parasites have enormous impact on human and animal health, particularly in the tropics, where there are serioous consequences for low-income economies. Different S-MGBs have activity against, for example:
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Plasmodium falciparum which causes malaria
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Leishmania donovani, transmitted by sand flies to humans and particularly problematic when patients are co-infected with HIV
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Trypanosoma congolense, infecting domesticated animals such as cattle, goats and camels
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Trypanosoma vivax, transmitted to cattle by tsetse flies
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Trypanosoma brucei also transmitted by tsetse flies but causing sleepingsickness in cattle and humans
Many bacterial pathogens are difficult to treat and becoming ever more resistant to existing clinical antibiotics. S-MGBs have activity against, for example:
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Mycobacterium tuberculosis for which Extreme Drug Resistant (XDR) strain have increased in prevalence
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Staphylococcus aureus, including methicillin-resistant isolates (MRSA)