Potential of application of the RNA interference phenomenon in the treatment of new coronavirus infection COVID-19

Cover Page

Cite item

Full Text

Abstract

COVID-19 has killed more than 4 million people to date and is the most significant global health problem. The first recorded case of COVID-19 had been noted in Wuhan, China in December 2019, and already on March 11, 2020, World Health Organization declared a pandemic due to the rapid spread of this infection. In addition to the damage to the respiratory system, SARS-CoV-2 is capable of causing severe complications that can affect almost all organ systems. Due to the insufficient effectiveness of the COVID-19 therapy, there is an urgent need to develop effective specific medicines. Among the known approaches to the creation of antiviral drugs, a very promising direction is the development of drugs whose action is mediated by the mechanism of RNA interference (RNAi). A small interfering RNA (siRNA) molecule suppresses the expression of a target gene in this regulatory pathway. The phenomenon of RNAi makes it possible to quickly create a whole series of highly effective antiviral drugs, if the matrix RNA (mRNA) sequence of the target viral protein is known. This review examines the possibility of clinical application of siRNAs aimed at suppressing reproduction of the SARS-CoV-2, taking into account the experience of similar studies using SARS-CoV and MERS-CoV infection models. It is important to remember that the effectiveness of siRNA molecules targeting viral genes may decrease due to the formation of viral resistance. In this regard, the design of siRNAs targeting the cellular factors necessary for the reproduction of SARS-CoV-2 deserves special attention.

About the authors

E. A. Pashkov

FSAEI HE I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of the Health of Russia; FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Author for correspondence.
Email: pashckov.j@yandex.ru
ORCID iD: 0000-0002-5682-4581

Evgeny A. Pashkov, Junior Researcher of the Molecular Immunology Laboratory; Postgraduate Student of the Department of Microbiology, Virology, and Immunology

119991, Moscow, Russia

105064, Moscow, Russia

Russian Federation

E. R. Korchevaya

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: fake@neicon.ru
ORCID iD: 0000-0002-6417-3301

105064, Moscow, Russia

Russian Federation

E. B. Faizuloev

FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: fake@neicon.ru
ORCID iD: 0000-0001-7385-5083

105064, Moscow, Russia

Russian Federation

O. A. Svitich

FSAEI HE I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of the Health of Russia; FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: fake@neicon.ru
ORCID iD: 0000-0003-1757-8389

119991, Moscow, Russia

105064, Moscow, Russia

Russian Federation

E. P. Pashkov

FSAEI HE I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of the Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-2581-273X

119991, Moscow, Russia

Russian Federation

D. N. Nechaev

FSAEI HE I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of the Health of Russia

Email: fake@neicon.ru
ORCID iD: 0000-0002-7592-3809

119991, Moscow, Russia

Russian Federation

V. V. Zverev

FSAEI HE I.M. Sechenov First Moscow State Medical University (Sechenov University) of the Ministry of the Health of Russia; FSBRI «I.I. Mechnikov Research Institute of Vaccines and Sera»

Email: fake@neicon.ru
ORCID iD: 0000-0002-0017-1892

119991, Moscow, Russia

105064, Moscow, Russia

Russian Federation

References

  1. WHO. Coronavirus (COVID-19) Dashboard. Coronavirus Disease (COVID-19) Dashboard. Available at: https://covid19.who.int/ (accessed July 29, 2021).
  2. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020; 5(4): 536–44. https://doi. org/10.1038/s41564-020-0695-z
  3. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020. Available at: https://www.who.int/ru/dg/ speeches/detail/who-director-general-s-opening-remarks-at-the-me dia-briefing-on-covid-19---11-march-2020 (accessed July 29, 2021).
  4. Hanff T.C., Harhay M.O., Brown T.S., Cohen J.B., Mohareb A.M. Is there an association between COVID-19 mortality and the renin angiotensin system? A call for epidemiologic investigations. Clin. Infect. Dis. 2020; 71(15): 870–4. https://doi.org/10.1093/cid/ciaa329
  5. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497–506. https://doi.org/10.1016/ s0140-6736(20)30183-5
  6. Wu J., Li J., Zhu G., Zhang Y., Bi Z., Yu Y., et al. Clinical features of maintenance Hemodialysis patients with 2019 novel Coronavi rus-infected pneumonia in Wuhan, China. Clin. J. Am. Soc. Nephrol. 2020; 15(8): 1139–45. https://doi.org/10.2215/cjn.04160320
  7. Mao L., Jin H., Wang M., Hu Y., Chen S., He Q., et al. Neurologic manifestations of hospitalized patients with Coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6): 683–90. https:// doi.org/10.1001/jamaneurol.2020.1127
  8. Perico L., Benigni A., Remuzzi G. Should COVID-19 concern nephrologists? Why and to what extent? The emerging impasse of angiotensin blockade. Nephron. 2020; 144(5): 213–21. https://doi. org/10.1159/000507305
  9. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. 2020; 8(4): 420–2. https://doi. org/10.1016/s2213-2600(20)30076-x
  10. Jordan R.E., Adab P., Cheng K.K. Covid-19: risk factors for severe disease and death. BMJ. 2020; 368: m1198. https://doi.org/10.1136/ bmj.m1198
  11. Coronavirus disease 2019 (COVID-19). Complications. Available at: https://bestpractice.bmj.com/topics/en-gb/3000201/complications (accessed July 29, 2021).
  12. Yasuhara J., Kuno T., Takagi H., Sumitomo N. Clinical characteristics of COVID-19 in children: A systematic review. Pediatr. Pulmonol. 2020; 55(10): 2565–75. https://doi.org/10.1002/ppul.24991
  13. Panigrahy N., Policarpio J., Ramanathan R. Multisystem inflammatory syndrome in children and SARS-CoV-2: A scoping re view. J. Pediatr. Rehabil. Med. 2020; 13(3): 301–16. https://doi. org/10.3233/prm-200794
  14. García-Salido A., de Carlos Vicente J.C., Belda Hofheinz S., Balcells Ramírez J., Slöcker Barrio M., Leóz Gordillo I., et al. Spanish Pediatric Intensive Care Society working group on SARS-CoV-2 infection. Severe manifestations of SARS-CoV-2 in children and adolescents: from COVID-19 pneumonia to multisystem inflammatory syndrome: a multicentre study in pediatric intensive care units in Spain. Crit. Care. 2020; 24(1): 666. https://doi.org/10.1186/ s13054-020-03332-4
  15. Cao B., Wang Y., Wen D., Liu W., Wang J., Fan G., et al. A trial of Lopinavir–Ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med. 2020; 382(19): 1787–99. https://doi.org/10.1056/ nejmoa2001282
  16. Joshi S., Parkar J., Ansari A., Vora A., Talwar D., Tiwaskar M., et al. Role of favipiravir in the treatment of COVID-19. Int. J. Infect. Dis. 2021; 102: 501–8. https://doi.org/10.1016/j.ijid.2020.10.069
  17. Cavalcanti A.B., Zampieri F.G., Rosa R.G., Azevedo L.C.P., Veiga V.C., Avezum A., et al. Hydroxychloroquine with or without azithromycin in mild-to-moderate Covid-19. N. Engl. J. Med. 2020; 383(21): 2041–52. https://doi.org/10.1056/NEJMoa2019014
  18. Sa Ribero M., Jouvenet N., Dreux M., Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020; 16(7): e1008737. https://doi.org/10.1371/journal.ppat.1008737
  19. Онищенко Г.Г., Сизикова Т.Е., Лебедев В.Н., Борисевич С.В. Анализ перспективных направлений создания вакцин против COVID-19. БИОпрепараты. Профилактика, диагностика, лечение. 2020; 20(4): 216–27. https://doi.org/10.30895/2221- 996X-2020-20-4-216-227
  20. Glover R.E., Urquhart R., Lukawska J., Blumenthal K.G. Vaccinating against covid-19 in people who report allergies. BMJ. 2021; 372: n120. https://doi.org/10.1136/bmj.n120
  21. Smith M. Vaccine safety: medical contraindications, myths, and risk communication. Pediatr. Rev. 2015; 36(6): 227–38. https://doi. org/10.1542/pir.36-6-227
  22. Gallup. One in Three Americans Would Not Get COVID-19 Vaccine. Available at: https://news.gallup.com/poll/317018/one three-americans-not-covid-vaccine.aspx (accessed July 29, 2021).
  23. da Costa C.B.P., Martins F.J., da Cunha L.E.R., Ratcliffe N.A., Cisne de Paula R., Castro H.C. COVID-19 and Hyperimmune sera: A feasible plan B to fight against coronavirus. Int. Immunopharmacol. 2021; 90: 107220. https://doi.org/10.1016/j.intimp.2020.107220
  24. Weng Y., Xiao H., Zhang J., Liang X.J., Huang Y. RNAi therapeutic and its innovative biotechnological evolution. Biotechnol. Adv. 2019; 37(5): 801–25. https://doi.org/10.1016/j.biotechadv.2019.04.012
  25. Janssen H.L., Reesink H.W., Lawitz E.J., Zeuzem S., Rodriguez Torres M., Patel K., et al. Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 2013; 368(18): 1685–94. https://doi. org/10.1056/nejmoa1209026
  26. Qureshi A., Tantray V.G., Kirmani A.R., Ahangar A.G. A review on current status of antiviral siRNA. Rev. Med. Virol. 2018; 28(4): e1976. https://doi.org/10.1002/rmv.1976
  27. Hoy S.M. Patisiran: first global approval. Drugs. 2018; 78(15): 1625–31. https://doi.org/10.1007/s40265-018-0983-6
  28. Center for drug evaluation and research. Multi-discipline review. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/ nda/2019/212194Orig1s000MultidisciplineR.pdf (accessed July 29, 2021).
  29. Agrawal N., Dasaradhi P.V., Mohmmed A., Malhotra P., Bhatnagar R.K., Mukherjee S.K. RNA interference: biology, mechanism, and applications. Microbiol. Mol. Biol. Rev. 2003; 67(4): 657
  30. Fire A., Xu S.Q., Montgomery M.K., Kostas S.A., Driver S.E., Mel lo C.C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998; 391(6669): 806–11. https://doi.org/10.1038/35888
  31. Пашков Е.А., Файзулоев Е.Б., Свитич О.А., Сергеев О.В., Зверев В.В. Перспектива создания специфических противогриппозных препаратов на основе синтетических малых интерферирующих РНК. Вопросы вирусологии. 2020; 65(4): 182–90. https://doi.org/10.36233/0507-4088-2020-65-4-182-190
  32. Kannan S., Shaik Syed Ali P., Sheeza A., Hemalatha K. COVID-19 (Novel Coronavirus 2019) – recent trends. Eur. Rev. Med. Pharmacol. Sci. 2020; 24(4): 2006–11. https://doi.org/10.26355/ eurrev_202002_20378
  33. Nur S.M., Hasan M.A., Amin M.A., Hossain M., Sharmin T. Design of potential RNAi (miRNA and siRNA) molecules for Middle East respiratory syndrome coronavirus (MERS-CoV) gene silencing by computational method. Interdiscip. Sci. 2015; 7(3): 257–65. https:// doi.org/10.1007/s12539-015-0266-9
  34. Zhou P., Yang X.L., Wang X.G., Hu B., Zhang L., Zhang W., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798): 270–3. https://doi. org/10.1038/s41586-020-2012-7
  35. Meng B., Lui Y.W., Meng S., Cao C., Hu Y. Identification of effective siRNA blocking the expression of SARS viral envelope E and RDRP genes. Mol. Biotechnol. 2006; 33(2): 141–8. https://doi. org/10.1385/mb:33:2:141
  36. Wang Y., Cao Y.L., Yang F., Zhang Y., Wang S.H., Liu L. Small interfering RNA effectively inhibits the expression of SARS corona virus membrane gene at two novel targeting sites. Molecules. 2010; 15(10): 7197–207. https://doi.org/10.3390/molecules15107197
  37. Zhao P., Qin Z.L., Ke J.S., Lu Y., Liu M., Pan W., et al. Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles. FEBS Lett. 2005; 579(11): 2404–10. https://doi.org/10.1016/j.febslet.2005.02.080
  38. Wang Z., Ren L., Zhao X., Hung T., Meng A., Wang J., et al. Inhibition of severe acute respiratory syndrome virus replication by small interfering RNAs in mammalian cells. J. Virol. 2004; 78(14): 7523–7. https://doi.org/10.1128/jvi.78.14.7523-7527.2004
  39. Shi Y., Yang D.H., Xiong J., Jia J., Huang B., Jin Y.X. Inhibition of genes expression of SARS coronavirus by synthetic small interfer ing RNAs. Cell Res. 2005; 15(3): 193–200. https://doi.org/10.1038/ sj.cr.7290286
  40. Xiao X., Dimitrov D.S. The SARS-CoV S glycoprotein. Cell Mol. Life Sci. 2004; 61(19-20): 2428–30. https://doi.org/10.1007/ s00018-004-4257-y
  41. Wu C.J., Huang H.W., Liu C.Y., Hong C.F., Chan Y.L. Inhibition of SARS-CoV replication by siRNA. Antiviral. Res. 2005; 65(1): 45–8. https://doi.org/10.1016/j.antiviral.2004.09.005
  42. Qin Z.L., Zhao P., Zhang X.L., Yu J.G., Cao M.M., Zhao L.J., et al. Silencing of SARS-CoV spike gene by small interfering RNA in HEK 293T cells. Biochem. Biophys. Res. Commun. 2004; 324(4): 1186–93. https://doi.org/10.1016/j.bbrc.2004.09.180
  43. Chen Z., Zhang L., Qin C., Ba L., Yi C.E., Zhang F., et al. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J. Virol. 2005; 79(5): 2678–88. https://doi.org/10.1128/ jvi.79.5.2678-2688.2005
  44. Qin C., Wang J., Wei Q., She M., Marasco W.A., Jiang H., et al. An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus. J. Pathol. 2005; 206(3): 251-9. https://doi. org/10.1002/path.1769
  45. Haasnoot P.C., Cupac D., Berkhout B. Inhibition of virus replica tion by RNA interference. J. Biomed. Sci. 2003; 10(6 Pt. 1): 607–16. https://doi.org/10.1159/000073526
  46. Zheng B.J., Guan Y., Tang Q., Du C., Xie F.Y., He M.L., et al. Prophylactic and therapeutic effects of small interfering RNA targeting SARS-coronavirus. Antivir. Ther. 2004; 9(3): 365–74.
  47. Ghanayem N.S., Yee L., Nelson T., Wong S., Gordon J.B., Marcdante K., et al. Stability of dopamine and epinephrine solutions up to 84 hours. Pediatr. Crit. Care. Med. 2001; 2(4): 315–7. https://doi. org/10.1097/00130478-200110000-00005
  48. Thomas N.J., Hollenbeak C.S., Lucking S.E., Willson D.F. Cost-effectiveness of exogenous surfactant therapy in pediat ric patients with acute hypoxemic respiratory failure. Pediatr. Crit. Care Med. 2005; 6(2): 160–5. https://doi.org/10.1097/01. pcc.0000154965.08432.16
  49. Li B.J., Tang Q., Cheng D., Qin C., Xie F.Y., Wei Q., et al. Using siRNA in prophylactic and therapeutic regimens against SARS coronavirus in Rhesus macaque. Nat. Med. 2005; 11(9): 944–51. https://doi.org/10.1038/nm1280
  50. Åkerström S., Mirazimi A., Tan Y.J. Inhibition of SARS-CoV rep lication cycle by small interference RNAs silencing specific SARS proteins, 7a/7b, 3a/3b and S. Antiviral Res. 2007; 73(3): 219–27. https://doi.org/10.1016/j.antiviral.2006.10.008
  51. Gallicano G.I., Casey J.L., Fu J., Mahapatra S. Molecular targeting of vulnerable RNA sequences in SARS CoV-2: identifying clinical feasibility. Gene Ther. 2020; 1–8. https://doi.org/10.1038/s41434- 020-00210-0
  52. Sohrab S.S. et al. Antiviral Activity Evaluation of siRNAs Against MERS-CoV in Vero Cell Culture. Applied Microbiology. London; 2020.
  53. Millet J.K., Whittaker G.R. Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activa tion of the spike protein. Proc. Natl. Acad. Sci. USA. 2014; 111(42): 15214–9. https://doi.org/10.1073/pnas.1407087111
  54. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003; 426(6965): 450–4. https://doi. org/10.1038/nature02145
  55. Lu C.Y., Huang H.Y., Yang T.H., Chang L.Y., Lee C.Y., Huang L.M. siRNA silencing of angiotensin-converting enzyme 2 reduced severe acute respiratory syndrome-associated coronavirus replications in Vero E6 cells. Eur. J. Clin. Microbiol. Infect. Dis. 2008; 27(8): 709–15. https://doi.org/10.1007/s10096-008-0495-5
  56. Hanff T.C., Harhay M.O., Brown T.S., Cohen J.B., Mohareb A.M. Is There an Association Between COVID-19 Mortality and the Re nin-Angiotensin System? A Call for Epidemiologic Investigations. Clin. Infect. Dis. 2020; 71(15): 870–4. https://doi.org/10.1093/cid/ ciaa329
  57. Cheng H., Wang Y., Wang G.Q. Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19. J. Med. Virol. 2020; 92(7): 726–30. https://doi. org/10.1002/jmv.25785
  58. de Wilde A.H., Wannee K.F., Scholte F.E., Goeman J.J., Ten Dijke P., Snijder E.J., et al. A kinome-wide small interfering RNA screen identifies proviral and antiviral host factors in severe acute respiratory syndrome coronavirus replication, including double-stranded RNA-activated protein kinase and early secretory pathway proteins. J. Virol. 2015; 89(16): 8318–33. https://doi.org/10.1128/jvi.01029-15
  59. de Wilde A.H., Snijder E.J., Kikkert M., van Hemert M.J. Host factors in coronavirus replication. Curr. Top. Microbiol. Immunol. 2018; 419: 1–42. https://doi.org/10.1007/82_2017_25

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Pashkov E.A., Korchevaya E.R., Faizuloev E.B., Svitich O.A., Pashkov E.P., Nechaev D.N., Zverev V.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».