Rosa Rubicondior: Malevolent Design - How Sudan Virus is Cleverly Designed to Kill 50% of Its Victims

Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1

New Study Reveals How Sudan Virus Binds to Human Cells | Midwest Antiviral Drug Discovery (AViDD) Center

It's shaping up to be a thrilling month for devotees of creationism's divine malevolence as science finds out just how brilliantly its nasty little parasites are designed to make us sick and increase the suffering in the world, although quite why any normal person would worship a hate-filled sadistic psychopath is even more of a mystery than the mechanism by which it designs and creates organisms.

The latest is the details of how the Sudan virus (a variant of Ebola with a 50% 'success' rate in terms of deaths of its victims) has an improved method of binding to our cells to gain entry and start the killing process. Like Ebola, it binds to receptors on the cell surface, but because it has just 4 different amino acids in its coat proteins, it binds much more efficiently - a factor which probably contributes to its high kill rate.

What can you tell me about the Sudan variant of ebola, known as the Sudan virus? The Sudan virus (Sudan ebolavirus or SUDV) is one of the six known species of Ebolavirus and is responsible for Sudan virus disease (SVD), a form of viral Heamorrhagic fever similar to Ebola virus disease (EVD). It was first identified in 1976 during simultaneous outbreaks in Sudan and the Democratic Republic of the Congo (formerly Zaire).

Key Characteristics of Sudan Virus

Classification: A member of the Filoviridae family and Ebolavirus genus.
Mortality Rate: Historically varies between 41% and 100%, with an average of about 50%, making it slightly less lethal than Zaire ebolavirus (Ebola virus), which can reach a mortality rate of 90%.
Transmission: Spread through direct contact with bodily fluids (blood, saliva, vomit, faeces, urine, sweat, breast milk, and semen) of infected individuals, contaminated surfaces, or infected animals (likely bats or non-human primates).
Symptoms: Fever, severe headache, muscle pain, fatigue, vomiting, diarrhea, abdominal pain, unexplained bleeding or bruising, and multi-organ failure in severe cases.
Outbreaks
Sudan virus has caused multiple outbreaks, primarily in Central and East Africa:

1976 (Sudan) – First recorded outbreak, with a 53% fatality rate.
1979 (Sudan) – Second outbreak, with a 65% fatality rate.
2000-2001 (Uganda) – Large outbreak with 425 cases and 224 deaths (fatality rate ~53%).
2012 (Uganda) – Two outbreaks, with a combined 17 deaths.
2022 (Uganda) – A major outbreak with over 140 cases and a mortality rate of ~55%.
Prevention and Treatment

No Licensed Vaccine (as of 2025): Unlike Zaire ebolavirus, which has an approved vaccine (Ervebo), there is no fully approved vaccine for Sudan virus. However, experimental vaccines (e.g., from Oxford University and the Sabin Vaccine Institute) have been in development and tested in response to recent outbreaks.
Supportive Care: Treatment is mainly supportive, including intravenous fluids, oxygen therapy, pain management, and treatment for secondary infections.
Experimental Therapies: Monoclonal antibodies and antiviral drugs are being researched, but none are yet widely available.
Since Sudan virus has significant outbreak potential and a high fatality rate, it remains a major concern for global health organizations such as the WHO and CDC.

And, because this gives the virus such an advantage in terms of its ability to replicate, we can exclude Michael J. Behe's scientifically nonsensical excuse of 'devolution'. We also have to include William A. Dembski's 'proof' of intelligent design because the virus’s genome has functional complexity and is therefore, according to Dembski, 'specified' by an intelligent designer. So, the conclusion, from a creationist perspective, is that this virus was designed by creationist’s intelligent [sic] designer to make us sick and kill up to 50% of its victims.

How this was discovered is the subject of a research paper by a team of researchers led by Professor Dr. Fang Li, co-director of the Midwest AViDD Center and professor of Pharmacology at Minnesota University, Minneapolis/St. Paul, MN, USA, in Communications Biology and a Minnesota University news release:

New Study Reveals How Sudan Virus Binds to Human Cells
MINNEAPOLIS/ST. PAUL (02/03/2025) –The Sudan virus, a close relative of Ebola, has a fatality rate of 50% but remains poorly understood in terms of how it infects cells. Currently, no approved treatments exist. To address this critical gap in pandemic preparedness, researchers at the University of Minnesota and the Midwest Antiviral Drug Discovery (AViDD) Center investigated how this deadly virus attaches to human cells.
Like Ebola, the Sudan virus enters cells by binding to NPC1, a protein responsible for cholesterol transport. Using cryo-electron microscopy, the researchers mapped how the Sudan virus interacts with the human NPC1 receptor. Their findings revealed that four key amino acid differences in the receptor-binding proteins of Sudan and Ebola viruses enable the Sudan virus to bind to human NPC1 with nine times greater affinity than Ebola, which may contribute to its high fatality rate.

Building on this discovery, the team predicted the receptor-binding affinities of three other filoviruses closely related to Sudan and Ebola. They also examined how the Sudan virus binds to NPC1 receptors in bats, which are believed to be natural hosts of filoviruses. These findings provide crucial insights into the infection mechanisms and evolutionary origins of Sudan virus and related filoviruses, paving the way for potential treatments.

Published in Communications Biology, the study was led by Dr. Fang Li, co-director of the Midwest AViDD Center and professor of Pharmacology. The research team included graduate student Fan Bu, research scientist Dr. Gang Ye, research assistants Hailey Turner-Hubbard and Morgan Herbst (Department of Pharmacology), and Dr. Bin Liu (Hormel Institute).

Abstract
Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unclear. This study compares the glycoproteins of SUDV and EBOV (in their proteolytically primed forms) and their binding to human NPC1 (hNPC1). The findings reveal that the SUDV glycoprotein binds significantly more strongly to hNPC1 than the EBOV glycoprotein. Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it. Collectively, these residue differences account for SUDV’s stronger binding affinity for hNPC1. This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range.

Introduction
The ebolavirus genus, part of the filovirus family, comprises five distinct viruses, four of which are capable of infecting humans¹. Bats are believed to be the natural reservoir for ebolaviruses, and animal-to-human transmissions have led to sporadic ebolavirus outbreaks, though no intact ebolaviruses have been isolated from bats or other animals^2,3. Among the five ebolaviruses, Ebola virus (EBOV) is the most prevalent and has caused the highest number of human fatalities^4,5. Sudan virus (SUDV), the second most prevalent ebolavirus, also poses a significant threat to global health and national security, having caused several recent outbreaks with a case fatality rate approaching 50%⁶. The most recent SUDV outbreaks occurred in Uganda between 2022 and 2023, resulting in 164 cases⁷. This outbreak highlights our ongoing vulnerability, as there is currently no FDA-approved vaccine or therapeutic for SUDV, unlike EBOV. Research on SUDV has been relatively limited, particularly in understanding its receptor recognition and cell entry mechanisms, which are crucial for evaluating its infectivity, tissue tropism, and host range, and for developing vaccines and treatments⁸. This study aims to address these gaps through a combination of structural biology, biochemistry, and sequence analysis.

The glycoprotein (GP) of ebolaviruses guides viral entry into host cells⁹. It assembles as a homotrimer on the virus surface, consisting of three copies each of the receptor-binding subunit GP1 and the membrane-fusion subunit GP2¹⁰. During maturation, the trimeric GP is cleaved at the GP1/GP2 junction by the protease furin, but GP1 and GP2 remain connected through a disulfide bond and noncovalent interactions. Each GP1 subunit contains a receptor-binding site (RBS), which is initially covered by a glycan cap and a mucin-like domain (MLD)^9,11. To enable entry, GP1 first attaches to nonspecific cell-surface factors, allowing the virus to be internalized via endocytosis¹². Once inside the endosomes, endosomal proteases remove the glycan cap and MLD, resulting in GPcl (the cleaved form of GP) and exposing the RBS¹³. The exposed RBS then binds to Niemann-Pick C1 (NPC1), the ebolavirus receptor on the endosomal membrane^14,15,16. Following this, GP2 undergoes dramatic conformational changes, fusing the viral and endosomal membranes to release the viral genome into the host cell’s cytoplasm^17,18.

NPC1 serves as the endosomal receptor for ebolaviruses and is essential for viral entry into cells^14,15,16. This transmembrane protein is widely expressed throughout the human body and is predominantly localized in late endosomes and lysosomes. A previous study resolved the cryo-EM structure of EBOV GPcl complexed with full-length human NPC1, demonstrating that the second luminal domain of NPC1, known as Domain C (NPC1-C), is responsible for binding filoviruses¹⁵. Another study determined the crystal structure of EBOV GPcl bound to NPC1-C, revealing that NPC1-C interacts with the receptor-binding site (RBS) of EBOV GPcl, located in a hydrophobic pocket, through two protruding loops - Loop 1 and Loop 2¹⁶. Interestingly, the binding affinity between NPC1-C and EBOV GPcl is relatively weak, with a dissociation constant (Kd) of about 100 µM¹⁶, much weaker than the binding affinities of receptors for other viruses, such as coronaviruses, which bind in the nanomolar range^19,20,21,22. This raises questions about how efficiently EBOV can infect tissues with low NPC1 expression. The structural interaction between SUDV and NPC1 has not yet been experimentally characterized. Additionally, the impact of sequence variations among different ebolaviruses on their binding affinity to human NPC1 remains unknown, limiting our understanding of receptor recognition and cell entry mechanisms for other ebolaviruses. Furthermore, it is unclear how genetic variations in NPC1 across different host species affect the host range of ebolaviruses. Previous studies have shown that NPC1 from African straw-colored fruit bats (Eidolon helvum) is recognized by SUDV, but only poorly by EBOV, due to a single amino acid difference between human NPC1 and that of E. helvum bats²³. The molecular mechanism behind this observation is not yet understood. Therefore, understanding the structural interaction between SUDV GP and NPC1 is crucial for better insights into receptor recognition, cell entry, tissue tropism, and host range of not only SUDV but also other ebolaviruses.

In this study, we compared the binding affinities of SUDV GPcl and EBOV GPcl to human NPC1-C and determined the structure of the SUDV GPcl complexed with human NPC1-C, the first such structure to our knowledge. From this structure, we identified key residue differences between SUDV and EBOV GPs that influence their differential binding to human NPC1. Biochemical studies were performed to validate our structural findings. Using these insights, we analyzed GP sequences from various ebolaviruses and examined sequence variations between human and bat NPC1. Collectively, these analyses provide a deeper understanding of receptor recognition, cell entry, tissue tropism, and host range across the ebolavirus genus.

Just another example of a pathogen being malevolently designed, if we accept creationist assertions for the sake of argument, which can't rationally be blamed on 'sin' or whatever daft, biologically nonsensical, excuse Michael J. Behe, et al. can muster.

No wonder Discovery Institute flunkies are so reticent about parasites and pathogens, and not just for the understandable reason of embarrassment about their own parasitic lifestyle.

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