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

 

 

  • David Baker group This email address is being protected from spambots. You need JavaScript enabled to view it.  (Washington) group page

    They are running a citizen science project here

 

  • 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.

 

  • 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.

 

  • Elisa Fadda group This email address is being protected from spambots. You need JavaScript enabled to view it. (Maynooth University) group page

    Role of glycosylation in the SARS-CoV-2 spike protein opening mechanism, stability and ACE2 binding

    Research Team: Aoife M. Harbison, Carl A. Fogarty (MU)
    Collaborators: Prof M. Kuiper and Prof C. Morton (U. of Melbourne, CSIRO)

    The novel coronavirus (nCoV) responsible for the ongoing pandemic is closely related to the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused an outbreak in 2003 in Asia, with secondary sites in different parts of the world. As with SARS-CoV, nCoV’s infection is triggered by the interaction of between the viral spike (nCoV-S) protein, a heavily glycosylated homo-trimer, and the host-cell bound angiotensin-converting enzyme 2 (ACE2), which facilitates the fusion between the viral and the cellular membrane. In this project in collaboration with colleagues at the University of Melbourne, we will use equilibrium and non-equilibrium molecular dynamics simulations to determine the role of the glycan shield in nCoV’s mechanism of infection, starting from the nCoV-S conformational changes required for activation, to ACE2 recognition and binding, with the aim of highlighting exposed epitopes (protein and glycans) and different potential mechanistic weaknesses that can be targeted for the rapid development of diagnostic and therapeutic strategies.

 

  • Juan R. Perilla group This email address is being protected from spambots. You need JavaScript enabled to view it. (U. Delaware) group page

    General topic: Emergent properties and global dynamics of native SARS-CoV-2 virions. Project leaders: Juan R. Perilla (U. Delaware), Jodi Hadden (U. Delaware) and Tyler Reddy (Los Alamos National Laboratory).

    All-atom virus simulations Jodi A Hadden and Juan R Perilla Current Opinion in Virology, (32), 82-91 (2018) https://doi.org/10.1016/j.coviro.2018.08.007
    Molecular dynamics simulations of large macromolecular complexes Curr Opin Struct Biol. 31: 64–74 (2015) https://dx.doi.org/10.1016%2Fj.sbi.2015.03.007
    Physical properties of the HIV-1 capsid from all-atom molecular dynamics simulations Nature Commun. 8, 15959 (2017) https://dx.doi.org/10.1038/ncomms15959

 

  • Carol Parish group This email address is being protected from spambots. You need JavaScript enabled to view it. (University of Richmond) group page

    The Parish lab is using MD and free energy methods to evaluate small molecule affinities for the SARS-CoV-2 main protease MPro (6lu7). To date, we have generated 4 x 250ns trajectories for 9 different HIV-1 protease inhibitors. MMGBSA evaluations of these trajectories suggest that darunavir has more affinity than other HIV-1 antivirals. We are happy to share these results and trajectories. Preliminary findings have been reported on twitter.

    However, it should be noted that Johnson & Johnson is reporting yet-to-be published results showing that five days of darunavir and cobicistat were not effective in treating COVID-19. link

 

  • Jean-Philip Piquemal group This email address is being protected from spambots. You need JavaScript enabled to view it. (Sorbonne Universite) group page

    We are mainly focused on structural biology and virtual screening. For now, I am especially interested in discussing building "accurate" large scale atomistic models.

 

  • Marta Filizola group This email address is being protected from spambots. You need JavaScript enabled to view it. (Icahn School of Medicine at Mount Sinai) group page

    My lab is using a structure-based drug discovery approach to expand the range of potential medications to be tested in clinical trials as potential therapeutics against COVID-19. Specifically, we have identified small molecules that might disrupt the interaction between the SARS-CoV-2-surface spike protein and its angiotensin-converting enzyme 2 (ACE2) receptor, thus preventing virus entry into host cells, and therefore its infection.

 

  • 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.

 

  • Gerhard Hummer This email address is being protected from spambots. You need JavaScript enabled to view it. (Max Planck Institute for Biophysics)

    Are working on simulations of the virus membrane and exterior proteins and how they interact with existing drugs. A write up on their work can be found 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.