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Covid-19 Ongoing Projects Available Resources Links to Other info

 

ongoing

 

Virtual screening projects

 

Anti-virals

 

  • PostEra a large collaboration of experimentalists and theoriticians looking for new inhibitors link

 

  • Fernanda Duarte group This email address is being protected from spambots. You need JavaScript enabled to view it. (Oxford) group page
    We are exploring the binding and dynamics of the main cysteine protease with a range of organic compounds currently available for testing and which could be easily modified at Oxford. Project partners Garret Morris (Oxford) and Chris Schofield (Oxford). We are happy to join forces with others.

 

  • Edina Rosta group This email address is being protected from spambots. You need JavaScript enabled to view it. (King’s College London) group page

    We are working on structure-based inhibitor design against COVID-19 helicase. We plan to design inhibitors using computational methods, synthesise them and the test using various biochemical assays. Project partners are Andre Cobb (King's College) and Mark Sanderson (King's College). We have key expertise in successfully synthesizing drugs active against coronaviral targets link

    Any volunteers willing to help us, please do get in touch.

    Fanelli, R.; Berta, D.; Földes, T.; Rosta, E.; Atkinson, R. A.; Hofmann, H.-J.; Shankland, K. Cobb, A. J. A. Organocatalytic Access to a Cis-Cyclopentyl-γ-Amino Acid: An Intriguing Model of Selectivity and Formation of a Stable 10/12-Helix from the Corresponding Γ/α-Peptide. J. Am. Chem. Soc.2020, 142(3), 1382–1393. https://doi.org/10.1021/jacs.9b10861.

    Wang, Z.; Huang, J. D.; Wong, K. L.; Wang, P. G.; Zhang, H. J.; Tanner, J. A.; Spiga, O.; Bernini, A.; Zheng, B. J.; Niccolai, N. On the Mechanisms of Bananin Activity against Severe Acute Respiratory Syndrome Coronavirus. FEBS J.2011, 278(2), 383–389. https://doi.org/10.1111/j.1742-4658.2010.07961.x.

    Cook, N. J.; Li, W.; Berta, D.; Badaoui, M.; Ballandras-Colas, A.; Nans, A.; Kotecha, A.; Rosta, E.; Engelman, A. N.; Cherepanov, P. Structural Basis of Second-Generation HIV Integrase Inhibitor Action and Viral Resistance. Science (80-. ).2020, 367(6479), 806–810. https://doi.org/10.1126/science.aay4919.

    Dell’Isola, A.; McLachlan, M. M. W.; Neuman, B. W.; Al-Mullah, H. M. N.; Binks, A. W. D.; Elvidge, W.; Shankland, K.; Cobb, A. J. A. Synthesis and Antiviral Properties of Spirocyclic [1,2,3]-Triazolooxazine Nucleosides. Chem. Eur. J.2014, 20(37), 11685–11689. https://doi.org/10.1002/chem.201403560.

 

  • Phil Biggin group This email address is being protected from spambots. You need JavaScript enabled to view it. (Oxford) group page

    The Biggin group is applying its knowledge of absolute binding free energies to guide optimization of compounds against different targets of SARS-CoV-2 in two collaboration; one with IBM and the other with Fernanda Duarte, Chris Schofield, and Garret Morris. We are happy to collaborate and offer expertise in anyway we can.

 

  • Peter Bond group This email address is being protected from spambots. You need JavaScript enabled to view it. (A*STAR Research Institute) group page

    We are leveraging our experience in multiscale simulation studies of enveloped viruses such as dengue (link) to explore the fundamental dynamics of coronavirus envelope components, initially focused on the spike glycoprotein, towards the search for weak points in COVID-19 for potential therapeutic intervention and diagnostics development. Project partners Max Crispin (Southampton) and Syma Khalid (Southampton).

    1. Marzinek et al. (2020). Multiscale modelling and simulation of viruses. Curr. Opin. Struct. Biol. 61:146-52.
    2. Lim et al. (2019). Molecular basis of dengue virus serotype 2 morphological switch from 29°C to 37°C. PLoS Pathog. 15:e1007996.
    3. Chan et al. (2019). Dengue disease severity caused by elevated levels of secreted NS1 arising from a single T164S substitution. Science. Transl. Med. 11:eaat7726.
    4. Marzinek JK et al. (2016). Pushing the Envelope: Dengue Viral Membrane Coaxed into Shape by Molecular Simulations. Structure. 24:1410-20.
    5. Wirawan et al. (2019). Mechanism of enhanced immature dengue virus attachment to endosomal membrane induced by prM antibody. Structure. 27:253-67.

 

  • Rommie Amaro group This email address is being protected from spambots. You need JavaScript enabled to view it. (UCSD) group page

    The Amaro lab are working on the S protien, they have reported some observations on twitter

    Rommie's group are also leading efforts to build an all-atom model of the SARS-COV-2 virus envelope in collaboration with Syma Khalid, Elisa Fadda and Michael Feig. Some news of this effort is here.


  • Adrian Mulholland group This email address is being protected from spambots. You need JavaScript enabled to view it. (Bristol) group page

    We used MD simulations using HECBioSim resources characterized a potential interaction of the SARS-CoV-2 spike protein with human nicotinic acetylcholine receptors (Biophys. J. 2021), recently supported by experiments (Mol. Neurobiol. 2022). Simulations also contributed to the identification of a fatty acid binding pocket in the SARS-CoV-2 spike protein, a site that is potentially druggable (Science 2020, Angewandte 2021). MD simulations show that the spike binds linoleic acid, stabilizing a ‘locked’ conformation, reducing viral infectivity. We have simulated and analysed emerging spike variants (Nature Comms. 2022). We have also used simulations to investigate effects of pH in respiratory aerosols (bioRxiv 2021, International Journal of High Performance Computing Applications in press 2022).  Simulations also identified allosteric effects of linoleate on functional regions of the spike, e.g. the furin cleavage site (CSBJ 2022), which differ between variants (bioRxiv 2022).

 

  • Francesco Luigi Gervasio group This email address is being protected from spambots. You need JavaScript enabled to view it. (University College London) group page

    We are exploring cryptic binding sites and structure-based inhibitor design against COVID-19 Non-structural protein 1. We plan to use enhanced sampling and mixed solvent simulations to predict binding hotspots and cryptic binding sites and use this information to screen compound libraries and design inhibitors, synthesise and test in vitro using various biochemical assays.

 

  • Accellera

    Have been working on a project to show the binding of melatonin binding to SARS-COV-2 protease. They have released all data, tools and code to run these simulations here.

 

Vaccines

 

  • Michele Vendruscolo group This email address is being protected from spambots. You need JavaScript enabled to view it. (Cambridge) group page

    Simultaneous determination of the structure and dynamics of the SARS-CoV-2 spike using cryo-electron microscopy and metainference simulations

    1. A. C. Wallset al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell180, 1-12 (2020).
    2. M. Bonomi, R. Pellarin, M. Vendruscolo, Simultaneous determination of protein structure and dynamics using cryo-electron microscopy. Biophy. J. 114, 1604-1613 (2018).
    3. M. Bonomi, M. Vendruscolo, Determination of protein structural ensembles using cryo-electron microscopy. Curr. Op. Struct. Biol.56, 37-45 (2019).
    4. D. Wrappet al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science367, 1260-1263 (2020).

    Computational design of antibodies against the SARS-CoV-2 spike

    1. M. Bonomi, G. T. Heller, C. Camilloni, M. Vendruscolo, Principles of protein structural ensemble determination. Curr. Op. Struct. Biol. 42, 106-116 (2017).
    2. M. Bonomi, M. Vendruscolo, Determination of protein structural ensemblesusing cryo-electron microscopy. Curr. Op. Struct. Biol. 56, 37-45 (2019).
    3. A. C. Wallset al., Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell180, 1-12 (2020).
    4. D. Wrappet al., Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science367, 1260-1263 (2020).

 

Fundamental conformational dynamics of viral proteins

 

  • Mark Sansom group This email address is being protected from spambots. You need JavaScript enabled to view it. (Oxford) group page

    We are interested in Covid-19 membrane proteins, including the E protein.