Science Pool

Following chikungunya virus infection, chronic rheumatological symptoms are similar to those observed with rheumatoid arthritis. To further evaluate this, a comparison was made between the relevance of joint counts and symptoms between the two conditions.

In this publication, we focus on:

• a background to chikungunya virus and its various symptoms including chronic joint pain and inflammation
• a cross sectional study of 40 patients with chronic chikungunya arthralgia and 40 patients with rheumatoid arthritis in order to compare symptoms
• an assessment of the relevance of joint counts in both conditions and their relationship with disability

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The Hollow Fibre Infection Model (HFIM) is a dynamic in vitro system for the determination of  PK/PD relationships between antimicrobial compounds and bacteria, fungi or viruses.

Evotec has developed its own dedicated state-of-the-art BSL2 facility offering it partners a bespoke in vitro PK/PD service tailored to advance their individual antimicrobial development programs.

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The ‘core’ metabolome of the Bacteroidetes genus Chitinophaga was recently discovered to consist of only seven metabolites. A structural relationship in terms of shared lipid moieties among four of them was postulated. Here, structure elucidation and characterization via ultra-high resolution mass spectrometry (UHR-MS) and nuclear magnetic resonance (NMR) spectroscopy of those four lipids (two lipoamino acids (LAAs), two lysophosphatidylethanolamines (LPEs)), as well as several other undescribed LAAs and N-acyl amino acids (NAAAs), identified during isolation were carried out. 

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The need for antimalarial drugs is urgent in the face of growing resistance to existing therapies. Murithi et al. characterized MMV688533, an acylguanidine identified from compounds inhibiting known human drug targets that were screened for activity against Plasmodium falciparum

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In an unparalleled global effort, diagnostics and vaccines to identify and prevent Sars-CoV-2 infections have been made available to public health systems, with various therapeutics for acute cases of COVID-19 being currently tested in clinical trials.

Nevertheless, a significant research gap exists in the understanding and treatment of so-called Long COVID, i.e. the delayed onset of persistent health problems following a SARS-CoV-2 infection with mostly moderate to mild symptoms. While the resulting health economic implications still need to be assessed in the long term, it is already clear that affected patients suffer significantly from reduced quality of life and individual physical and mental performance.

Lessons from the Chikungunya Virus

In a recent letter to The Lancet, a team of researchers, including a scientist from Evotec Infectious Disease Group in Lyon, France, points out that politicians and the public often picture COVID-19 as a mono-phasic infection similar to the flu. This is an understandable cognitive bias as mode of transmission, clinical presentation and the explosive shape of the epidemic curve are all very similar to the flu, in particular the Spanish flu, a pandemic that 100 years ago killed 20-50 million people world-wide. However, the authors – familiar with the biphasic nature of chikungunya virus infections – see striking similarities not between COVID-19 and the flu but between COVID-19 and chikungunya (https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(21)00272-3/fulltext).

Chikungunya infections are spread by mosquito bites resulting in acute symptoms like fever and severe joint pain; headaches, muscle pain, swelling and rashes may be further symptoms. The infection is typically overcome within 1-2 weeks, but may cause lasting joint pain. However, it can also have serious long-term consequences and may lead to persistent mental or somatic constraints, causing both individual and economic burdens.

The researchers, therefore, call for a change in perspective when addressing COVID-19 and urge healthcare systems and politics to no longer ignore the biphasic nature of SARS-CoV-2 infections and its potential long-term disease course.

Antibody Treatments for Chikungunya Virus Infections - A Roadmap for COVID-19?

Evotec may contribute new data to allow a better understanding of fighting biphasic infections. However unlike COVID-19, there are currently no vaccines or treatments available to address chikungunya infections. To meet this medical need, the Company is developing EVT894, a first-in-class monoclonal antibody with anti-viral activity to treat and potentially prevent chikungunya virus infections, with the compound entering clinical development in late 2020.

EVT894 was derived from a patient who was infected with the chikungunya virus and shows promising data in pre-clinical testing, achieving potent neutralising activity in vitro and in vivo in both therapeutic and prophylactic disease models. It also demonstrated efficacy against all circulating chikungunya genotypes.

Future findings from the EVT894 studies may provide a blueprint for understanding - and, eventually, treating - biphasic infectious diseases such as chikungunya and COVID-19.

Further Background:

https://www.evotec.com/en/invest/news--announcements/p/evotec-starts-clinical-development-of-chikungunya-antibody-together-with-niaid-and-leading-academic-research-organisation-6020

Find out more about chikungunya:

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Alastair Parkes, Ph.D, Group Leader, Discovery Chemistry, Evotec UK

The problems surrounding the economics of antibacterial drug development are well known, with the cost of simply keeping a product available for use now outstripping revenues from sales in many cases.

However, early R&D push incentives from organisations such as CARB-X and the new AMR Action Fund are keeping research going, while efforts continue to try to ensure the true value of novel antibiotics are recognised, spearheaded by the UK’s pilot of a subscription model for reimbursement of developers of new antibiotics

The challenges of running clinical trials sufficient for approval and securing adequate sales returns can affect scientific strategy, resulting in the targeting of only broad-spectrum agents most desired by clinicians. Through years of research, and discussions with members of the antibacterial research community, it became clear to me that the understandable focus on what both regulators and the market will currently support can be at odds with some of the most promising avenues in the science of antibacterial drug discovery. Narrow spectrum or even single pathogen agents may be of huge value in years to come, and from a scientific perspective, these compounds may be more readily accessible than broad-spectrum drugs.

As a medicinal chemist, my primary focus is on molecular design, and while there are many excellent reviews in the field, I felt that a perspective addressing how the many aspects of antibacterial drug discovery affect our design strategies would be a useful addition. I visualise any problems from the viewpoint of the antibiotic molecule, and consider the various challenges it must overcome to become a useful agent for clearing bacterial infections. In each case I consider how our knowledge should influence design strategies. While these principles are at the heart of our research at Evotec, I hope that sharing these ideas with the wider community will aid researchers in their work to address the growing threat of AMR.

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Each year, more than 400 000 people die of malaria – a preventable and treatable life-threatening parasitic disease. Almost half the world’s population (about 3.2 billion people) are at risk of malaria with 229 million new malaria infections reported in 2019 and an estimated two thirds of deaths being among children under the age of 5.

The last 2 decades have seen a period of unprecedented progress in malaria control with the mortality rate dropping by up to 60% between 2000 and 2015 and a further 11 countries being officially certified as malaria free. The last 5 years however have seen a progress plateau, with senior health leaders calling for a renewed response to the treatment and prevention of malaria. The creation of new financing mechanisms, such as the Global Fund to Fight AIDS, Tuberculosis and Malaria and the EU Malaria Fund, together with robust political commitments has led to large scale deployment of malaria testing and access to artemisinin-based combination therapies (ACT’s), the recommended first line treatment for uncomplicated P.falciparum malaria.

However, malaria control is facing one of its greatest threats, an increasing trend of drug resistant parasites. ACT’s are used in most malaria endemic countries and remain a highly efficacious treatment, but with resistance confirmed in two of the four human malaria parasite species in areas of Southeast Asia and evidence of mutations linked to partial resistance in Africa, further spread of resistance could jeopardize important gains in the fight against malaria.

Working together for a malaria free world

In 2018, Evotec joined the fight to eliminate malaria and resistant pathogens with its acquisition of Sanofi’s infectious diseases R&D site in Lyon, France, with approximately 115 employees, a highly skilled and experienced infectious diseases team and an R&D portfolio in antibacterials, antivirals and global heath including tuberculosis and malaria.

Capabilities span from early drug discovery to clinical trials with proven experience of WHO recommendations, the specificities of antimalarial drugs, and target candidate/product profiles (TCP–TPP) as well as an extensive knowledge of the Plasmodium in vitro/in vivo models at all stages of the parasite life cycle.

Evotec’s highly experienced malaria team has access to a vast network of labs and organisations recognised for their expertise in antimalarial assays/models as well as internal PK/PD experts able to translate discovery data into appropriately designed antimalarial clinical trials.

Complementing this experience is an established leading-edge integrated anti-infective drug discovery platform, enabling the discovery and development of innovative new therapies to prevent and treat global life-threatening infections.

With the SARS-CoV2 pandemic representing a formidable challenge to malaria responses and the impact of this still being largely unknown, this World Malaria Day Evotec joins with other organisations to celebrate the achievements of countries that are approaching - and achieving malaria elimination #researchneverstops

Resources : World malaria report 2020, Final report of the E-2020 initiative

Contact info@evotec.com to speak with our malaria experts

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