{"id":5574,"date":"2020-03-03T18:56:27","date_gmt":"2020-03-03T18:56:27","guid":{"rendered":"https:\/\/www.blopig.com\/blog\/?p=5574"},"modified":"2021-06-22T15:36:10","modified_gmt":"2021-06-22T14:36:10","slug":"coronavirus","status":"publish","type":"post","link":"https:\/\/www.blopig.com\/blog\/2020\/03\/coronavirus\/","title":{"rendered":"Coronavirus"},"content":{"rendered":"\n

A zoonosis<\/em> is an infectious disease that has jumped from a non-human animal to humans.<\/p>\n\n\n\n

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A painting by David S. Goodsell showing coronavirus in pink and purple. Secreted mucus (greenish threads) and antibodies (yellow\/orange Y-shapes), and several small immune systems proteins (orange) from the lungs\u2019 respiratory cells surround it. \u00a9 2020, David S. Goodsell.<\/figcaption><\/figure>\n\n\n\n

The coronavirus disease 2019 (COVID-19<\/a>) is one such zoonosis, and is caused by severe acute respiratory syndrome coronavirus 2<\/a> (SARS coronavirus 2, SARS-CoV-2, or 2019-nCoV). This is very similar to the SARS<\/a> virus that emerged in 2003. Its recent emergence has resulted in a WHO-declared public health emergency of international concern<\/a>.<\/p>\n\n\n\n\n\n\n\n

Structural biologists are busy elucidating the structures of the molecular targets of coronavirus, as you can see at the Protein Data Bank. One such target is coronavirus protease<\/a>, which was featured in David Goodsell\u2019s Molecule of the Month column last month.<\/p>\n\n\n\n

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SARS-CoV-2 (2019-nCoV) coronavirus main protease, with inhibitor in turquoise. \u00a9 2020, David S. Goodsell.<\/figcaption><\/figure>\n\n\n\n

The blueprint for a coronavirus is stored in a long molecule\u2014a single strand of RNA<\/a>. If the virus is able to infect the right cell, it will hijack its molecular machinery, forcing it to synthesize two long polyproteins. A polyprotein is just another kind of long molecule, made up of amino acids<\/a> instead of nucleotides<\/a>. These polyproteins contain the molecular machines and molecular building blocks to make new virus particles (or ‘virions’) inside the infected cell.<\/p>\n\n\n\n

One of these molecular machines is the coronavirus main protease<\/em>, shown above. Its job is to make most of the cuts in the long polyproteins<\/a>. You can look at and download the structure of the coronavirus main protease of SARS-CoV-2 (or 2019-CoV) from the PDB, at entry 6lu7<\/a>. Coronavirus main protease is also known as COVID-19 coronavirus 3CL hydrolase (Mpro). In PDB entry 6lu7, it is complexed with an inhibitor:<\/p>\n\n\n\n

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A peptidomimetic inhibitor of coronavirus main protease, named N3<\/a>, or N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-L-valyl-N~1~-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide. This is a Michael acceptor<\/a>, and also happens to be an inhibitor of human SARS CoV main protease, and feline coronavirus main protease, see PDB entry 5eu8<\/a>.<\/figcaption><\/figure>\n\n\n\n

The amino acid sequence of COVID-19 coronavirus 3CL hydrolase (Mpro) shares a very high amino acid sequence identity (96%) with the SARS virus main protease (PDB entry 1q2w<\/a>). The World Wide Protein Data Bank has published a summary CSV<\/a> file of these closely-related PDB structures.<\/p>\n\n\n\n

The COVID-19 structures currently available in the PDB are:<\/p>\n\n\n\n