Biochem 冷知識系列 新冠口服藥異同！Comparison on COVID oral drugs!

係疫情來勢洶洶嘅時候，政府已經係4月中引入左新冠口服藥。係新冠口服藥嘅協助下，疫情嘅傷亡數字亦慢慢回落，但係香港就唔多新冠口服藥嘅資訊。有見及此，今日就等小編同大家介紹下 Paxlovid 同 Molnupiravir嘅異同啦！

As COVID oral drugs are introduced and applied into COVID medications in Hong Kong, let’s compare 2 applied drugs- Paxlovid from Pfizer and Molnupiravir!

係認識新冠口服藥嘅原理之前，我哋先睇下新冠病毒點樣入侵我哋嘅細胞。

How COVID-19 infect our cells?

1. 新冠病毒SARS-CoV-2有刺狀蛋白（Spike Protein），而人既細胞膜(cell membrane) 有ACE2受體（receptor）。ACE2受體會同新冠病毒刺狀蛋白合埋一齊，所以就會容許新冠病毒進入細胞。呢個正正就係新冠病毒最危險既地方，因為我地分辨唔到新冠病毒係病毒，所以新冠病毒潛伏期長，免疫力強既人未遇過新冠病毒都會中招。

2. 認左新冠病毒之後，個病毒就會融入人既細胞膜，病毒既基因RNA就係呢個時候進入細胞。

3. 呢個時候，病毒既RNA 會同時做兩件事：就係製造新病毒既組成部分（姐係製造蛋白質），同埋複製、包裝新病毒既RNA。

1. SARS-CoV-2 virus has spike proteins. The ACE2 receptor in human body cells recognizes spike proteins of SARS-CoV-2 virus.

2. After recognition, the virus is allowed to fuse with the cell by endocytosis (which is engulfing the virus). The viral RNA is entered into the cell.

3. The viral RNA will undergo 2 paths of process. One will undergo protein synthesis through transcription and translation, and the another will undergo viral RNA replication and packaging.

製造新病毒既組成部分（蛋白質製造）

4a. RNA 會透過核糖體（ribosome）做轉錄（Transcription）同轉譯（Translation）製造長既蛋白鏈（longer protein chain）。呢個長既蛋白鏈就會俾蛋白酶（protease）「剪短」成為短既蛋白鏈（shorter protein chain）。

5a. 呢啲短既蛋白鏈要變成真真正正有功能既蛋白質（protein），就要經過內質網（Endoplasmic reticulum, 簡稱ER）、ERGIC（ER-Golgi intermediate compartment，內質網同高爾基體之間既過渡區域，暫時冇中文名）同埋高爾基體（Golgi apparatus）進行蛋白質折疊（Protein folding）既過程。呢到有功能既蛋白質會成為新病毒既組成部分，包括前段提過既病毒刺狀蛋白。

Protein synthesis:

4a. After transcription and translation with ribosome, the RNA becomes long protein chain. This long protein chain will be cleaved by protease into shorter protein chains.

5a. The short protein chains will undergo protein folding process changing itself from a chain into a protein through ER, ERGIC and Golgic. These proteins will become the components of the virus, such as the spike protein of the virus.

病毒RNA 既複製

4b+5b. 病毒既RNA 會進行複製（replication）同埋蛋白質包裝（protein packaging）黎製造新既病毒RNA。

Viral RNA replication

4b + 5b. The viral RNA will undergo replication and protein packaging process to produce numerous viral RNAs.

6. 頭先製造左出黎新既病毒RNA 同埋新既組成部分就會會夾埋一齊，組成新既新冠病毒。

7. 呢個新既新冠病毒會透過出芽（budding）既方式係細胞入面走出黎，然後用同樣方式感染其他正常既細胞。

6. The new viral RNAs and synthesized proteins will assemble and form a new SARS-CoV-2 virus.

7. The virus will be expelled from the cell by exocytosis (budding), and infect other normal cells.

Paxlovid 既運作原理

How Paxlovid works?

Paxlovid 會抑制蛋白酶「剪短」蛋白鏈既功能，長既蛋白鏈就唔會變成短既蛋白鏈。冇左呢啲短既蛋白鏈，咁病毒既組成部分就唔會製造到出黎，病毒就自然製造唔到出黎啦！

Paxlovid inhibits protease action to cleave the long protein chains into shorter ones. Without short protein chains, different protein chains can’t be folded into viral components, therefore the virus is not assembled.

Molnupiravir既運作原理

How Molnupiravir works?

Molnupiravir 係RNA 複製過程入面，佢會係RNA編碼鏈（coding strand）同RNA 模板鏈（template strand）既A核苷酸（nucleotide）、G核苷酸夾埋一齊。因為Molnupiravir係苷類似物（Nucleotide analogs，姐係「裝假狗」既核苷酸），係下一條模板鏈組成既時候會比Molnupiravir「混淆視線」，咁複製病毒RNA 既時候就會出好多錯誤，新既病毒RNA 就冇辦法維持準確，甚至失去佢原本既病毒本質，新冠病毒亦都因為咁樣難以製造出黎啦。

Molnupiravir binds with A and G nucleotides of the RNA as the analog of A and G, therefore the next replication in next RNA template strand is disrupted since both A and G base can bind to the Molnupiravir, severe mutations are induced, normal viral genes are failed to maintain the fidelity and likely to lose its viral nature.

雖然兩隻新冠口服藥係有效，但係佢哋都有副作用架！

Both drugs contain side effects!

Paxlovid 會對部份常見藥物產生相互作用，包括薄血藥、抗生素和膽固醇藥等。如果病人要食Paxlovid呢隻藥，咁佢哋就要停止服食薄血藥、抗生素和膽固醇藥等藥物既療程，避免相互作用所帶黎既影響。

Paxlovid will have drug interactions with some known drugs, including anticoagulants, antibiotics and lipid lowering agents. Patients who are taking drugs including anticoagulants, antibiotics and lipid lowering agents in their ongoing treatment should stop their treatment to take the drug.

Molnupiravir可能會影響胎兒成長，所以孕婦或餵哺母乳既母親就唔好食Molnupiravir啦。

Molnupiravir may affect foetal development. Pregnant women and lactating mothers shouldn’t take this drug.

以上既資訊只係俾大家一個參考，如果你地想知多啲、或者考慮服食呢啲藥，請立即諮詢醫生既專業意見！

If you have any further enquires on the drug medication, please don’t hesitate to seek doctor’s professional advice! This post comprises different information of these drugs for your better knowledge.

如果大家鍾意呢類型既分享，記得俾個like, share 出去，或者話俾我知你地想知多啲關於biochem 既知識！我都係第一次整呢類型既post, 如果有改善/補充既地方麻煩你地幫手提醒～

If you find this post useful, please like and share this post!!! You may also ask for another sharing of biochemistry topics and knowledge too. This is my first time on designing knowledge-sharing post, please also comment below for suggestions~

Reference:

1. 2019冠狀病毒病專題網站 – 同心抗疫 – 居家隔離（包括尚待入院）人士須知. (2022, April 7). 2019冠狀病毒病專題網站. https://www.coronavirus.gov.hk/chi/tested-positive.html
2. COVID-19 Animation: What Happens If You Get Coronavirus? (2020, March 28). [Video]. YouTube. https://www.youtube.com/watch?v=5DGwOJXSxqg
3. Huang, Y. (2020, August 3). Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Nature. https://www.nature.com/articles/s41401-020-0485-4?error=cookies_not_supported&code=8cd4945d-2278-4b79-9862-0be529af9062#Fig1
4. Merck COVID Pill (Molnupiravir): A New Treatment Option? (Coronavirus Update 134). (2021, October 20). [Video]. YouTube. https://www.youtube.com/watch?v=aI0xGfITaas
5. Pfizer COVID 19 FDA Authorized Pill “Paxlovid” Explained. (2021, December 30). [Video]. YouTube. https://www.youtube.com/watch?v=GMMTw0MAT-8

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