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<b>Abstract</b>— <p>Coronaviruses, including the pandemic SARS-CoV-2, encode 16 non-structural proteins that regulate various stages of virus reproduction inside the infected cell but are not part of the virion structure. Some of these proteins are responsible for the formation of viroplasm, which is necessary for the reproduction of the viral genome. A characteristic feature of viroplasm is the formation of double-membrane vesicles, the physicochemical mechanisms of which are still unclear. At the same time, it is known that the non-structural protein 3 (nsp-3) plays an important role in this process. In this work, we showed that the X macrodomain (X-domain) of the nsp-3 protein of SARS-CoV-2 is capable of binding only to membranes containing acidic lipids. This domain forms various membrane tubulations, from filamentous to spherical, depending on the cholesterol content. Thus, X-domain of the nsp-3 protein of SARS-CoV-2 can be the initiator of the formation of double-membrane vesicles due to predominantly electrostatic interactions with membranes of cellular organelles.</p>

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X-Domain of nsp-3 Protein of the SARS-CoV-2 Coronavirus Is Capable of Deforming Membranes and Initiating of the Double-Membrane Vesicle Formation Depending on the Cholesterol Content

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • A. A. Makhonko,
  • Z. G. Denieva,
  • O. V. Batishchev

摘要

Abstract—

Coronaviruses, including the pandemic SARS-CoV-2, encode 16 non-structural proteins that regulate various stages of virus reproduction inside the infected cell but are not part of the virion structure. Some of these proteins are responsible for the formation of viroplasm, which is necessary for the reproduction of the viral genome. A characteristic feature of viroplasm is the formation of double-membrane vesicles, the physicochemical mechanisms of which are still unclear. At the same time, it is known that the non-structural protein 3 (nsp-3) plays an important role in this process. In this work, we showed that the X macrodomain (X-domain) of the nsp-3 protein of SARS-CoV-2 is capable of binding only to membranes containing acidic lipids. This domain forms various membrane tubulations, from filamentous to spherical, depending on the cholesterol content. Thus, X-domain of the nsp-3 protein of SARS-CoV-2 can be the initiator of the formation of double-membrane vesicles due to predominantly electrostatic interactions with membranes of cellular organelles.