rna, bir canlının tüm özelliklerini içeren kaynak kodudur. rna'da yazan bilgilerle yeni canlı hücreler oluşur.

sars-cov-2 virüsünün 30 bin harften oluşan bir genomu var. insan genomu ise 3 milyar harften oluşuyor. virüs, kanda gezerken denk geldiği insan hücresine dışarıdan yapışıyor. içeri giriyor. hücre yaşayan bir makine ve dışarıdan sızmalara karşı pek çok güvenlik önlemi var. ancak virüs içeri kafa karıştıran öyle moleküller bırakıyor ki hücre bir şeylerin yanlış gittiğini uzun süre anlamıyor, anladığında ise virüs hücrenin bağışıklık sistemine haber vermesini sağlayan sinyal sistemini bozduğu için her şey için geç kalınmış oluyor. bu noktaya varana kadar insan hücresi virüsün rna'sını kendi rna'sı sanarak defalarca çoğaltmış oluyor. hücre içine doluşan virüs kopyaları yine içeri salınan proteinin hücre duvarında açtığı delik ile kana geri karışıyorlar ve yeni hedeflerine yöneliyorlar.

virüsün 30 kilobyte olarak düşünebileceğimiz rna zinciri aşağıdaki işlevleri yerine getiren aygıtları içeriyor

- hücre içi sabotaj
- hücre içi yıkıma gidecek proteinlere müdahale etme
- kendini çoğaltmak için baloncuk oluşturma
- protein zincirlerini makaslayarak doğru yerlerinden kesme
- kendi rna'sını kopyalama
- hücre çekirdeğinde delikler açma (amacı henüz bilinmiyor)
- büzülmüş rna zincirini geri açma
- kendinin yanlış kopyalanmasının önüne geçen doğrulama mekanizması
- kendi kalıntılarını temizleyerek hücrenin savunmaya geçmesini engelleme
- kendini kamufle ederek hücre içi antivirüs sisteminin devreye girmesini engelleme
- kendi rna'sının etrafını saran proteinden oluşan dış kabuğu
- insan hücresine tutunmasına yarayan, dış kabuk üzeri çıkıntılar (corona yani taç ismi buradan geliyor)
- hücre içinden kaçış yolu için delik açarak dışarı çıkmak
- sinyal engelleme - hastalanmış hücrenin bağışıklık sistemine "beni kurtar" sinyali göndermesini engelleme

bu işlevlerin her biri hücre içine yerleştirilen değişik proteinler yardımıyla yapılıyor. aşağıda tek tek bu proteinleri oluşturan rna zincirlerini ve sonuç olarak virüsün rna kaynak kodunu göreceğiz.

açılış zinciri

virüs rna'sının ilk harflerine baktığımızda, bunun hücreyi "beni çoğalt" diye ikna eden bir zincir olduğunu görüyoruz. bu zinciri gören hücre gelen rna'nın kendisine ait olduğunu zannederek kopyasını yaratıyor:

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orf1ab protein zinciri

virüsün kullandığı çeşitli araçlar var. her biri ayrı olan bu 16 protein rna zincirinde bir arada duruyorlar. orf1ab zincirindeki iki protein bunları "makas" gibi birbirinden ayırarak alt protein rna'larının ortaya çıkmasını sağlıyor ve bu proteinler aşağıdaki işlevleri yerine getiriyorlar:

nsp1 proteini: hücre işlevlerini sabote etmek

insan hücresi hem işlemek hem de kendini korumak için pek çok mekanizmaya sahip. virüs bu hücrenin faaliyetlerini işlevsiz kılıyor ve sadece kendisini çoğaltmasını sağlıyor. nsp1 proteini hücrenin kendi proteinlerini üretmesini yavaşlatıyor, böylece hücre sadece virüsü kopyalayan basit bir makineye dönüşüyor.

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nsp2 proteini

henüz işlevi anlaşılmış değil. bir işlevi olmayabilir de. ancak virüs ile beraber geliyor ve hücre içine bırakılıyor.

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nsp3: rna kesip parçalama ve hücre işaretlemesini bozma

rna kesip parçalamayı yukarıda anlattık. virüs rna'sının alt parçalara ayrılması gerekiyor ve nsp3 bunu yapıyor ancak bu büyük proteinin bir işlevi daha var. insan hücresi artık işlevini yitirmiş ve yok edilmesi gereken proteinleri işaretleyen bir mekanizmaya sahip. nsp3 bu mekanizmayı bozuyor. böylece insan hücresinin işi yok edilmemiş ve istenmeyen proteinlerle doluyor. hücre sapıttığı için virüs ile mücadele edecek mekanizmaları devre dışı kalıyor.

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ccagucuucuuacaucguugauaguguuacagugaagaaugguuccauccaucuuuacuuugauaaagcuggucaaaagacuuaugaaagacauucucucucucauuuuguuaacuuagacaaccugagagcuaauaacacuaaagguucauugccuauuaauguuauaguuuuugaugguaaaucaaaaugugaagaaucaucugcaaaaucagcgucuguuuacuacagucagcuuaugugucaaccuauacuguuacuagaucaggcauuagugucugauguuggugauagugcggaaguugcaguuaaaauguuugaugcuuacguuaauacguuuucaucaacuuuuaacguaccaauggaaaaacucaaaacacuaguugcaacugcagaagcugaacuugcaaagaauguguccuuagacaaugucuuaucuacuuuuauuucagcagcucggcaaggguuuguugauucagauguagaaacuaaagauguuguugaaugucuuaaauugucacaucaaucugacauagaaguuacuggcgauaguuguaauaacuauaugcucaccuauaacaaaguugaaaacaugacaccccgugaccuuggugcuuguauugacuguagugcgcgucauauuaaugcgcagguagcaaaaagucacaacauugcuuugauauggaacguuaaagauuucaugucauugucugaacaacuacgaaaacaaauacguagugcugcuaaaaagaauaacuuaccuuuuaaguugacaugugcaacuacuagacaaguuguuaauguuguaacaacaaagauagcacuuaaggguggu

nsp4: baloncuk yaratan protein

bu protein hücre içinde minik sıvı dolu baloncuklar yaratıyor. bu baloncukların içinde virüsün oluşan kopyalarının parçaları inşa ediliyor.

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nsp5: diğer makas proteini

bu da rna üzerindeki parçaları birbirinden ayırarak bu listede yer alan proteinlerin oluşmasını sağlıyor.

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nsp6: baloncuk üretme proteini

nsp3 ve nsp4 ile beraber çalışarak virüsün kopya parçalarının oluştuğu baloncukları üretiyor.

agugcagugaaaagaacaaucaaggguacacaccacugguuguuacucacaauuuugacuucacuuuuaguuuuaguccagaguacucaauggucuuuguucuuuuuuuuguaugaaaaugccuuuuuaccuuuugcuauggguauuauugcuaugucugcuuuugcaaugauguuugucaaacauaagcaugcauuucucuguuuguuuuuguuaccuucucuugccacuguagcuuauuuuaauauggucuauaugccugcuaguugggugaugcguauuaugacaugguuggauaugguugauacuaguuugucugguuuuaagcuaaaagacuguguuauguaugcaucagcuguaguguuacuaauccuuaugacagcaagaacuguguaugaugauggugcuaggagaguguggacacuuaugaaugucuugacacucguuuauaaaguuuauuaugguaaugcuuuagaucaagccauuuccaugugggcucuuauaaucucuguuacuucuaacuacucagguguaguuacaacugucauguuuuuggccagagguauuguuuuuauguguguugaguauugcccuauuuucuucauaacugguaauacacuucaguguauaaugcuaguuuauuguuucuuaggcuauuuuuguacuuguuacuuuggccucuuuuguuuacucaaccgcuacuuuagacugacucuugguguuuaugauuacuuaguuucuacacaggaguuuagauauaugaauucacagggacuacucccacccaagaauagcauagaugccuucaaacucaacauuaaauuguuggguguugguggcaaaccuuguaucaaaguagccacuguacag

nsp7 ve nsp8: kopyalama asistanları

nsp12 ile beraber çalışarak hücre içinde oluşturulan virüs kopyalarının içine yerleştirilecek virüs rna'larını kopyalıyorlar.

nsp9 proteini: hücre çekirdeğine saldırı

insan hücresinin çekirdeğinde kendi genomumuz yer alır. nsp9 bu çekirdeğin duvarlarında delikler açar. bunun virüs'e faydası henüz anlaşılamamış.

aauaaugagcuuaguccuguugcacuacgacagaugucuugugcugccgguacuacacaaacugcuugcacugaugacaaugcguuagcuuacuacaacacaacaaagggagguagguuuguacuugcacuguuauccgauuuacaggauuugaaaugggcuagauucccuaagagugauggaacugguacuaucuauacagaacuggaaccaccuuguagguuuguuacagacacaccuaaagguccuaaagugaaguauuuauacuuuauuaaaggauuaaacaaccuaaauagagguaugguacuugguaguuuagcugccacaguacgucuacaa

nsp10 proteini: kamuflaj

insan hücresi antiviral proteinler içerir. bu proteinler içeri sızan virüs parçalarını bulur ve yok ederler. nsp10 proteini insan hücresinin bu işi yapmasına engel olur. antiviral mekanizma virüsü pas geçer.

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nsp12 proteini: kopyalama makinesi

virüsün yeni rna'larının oluşturulması işlevini görür. çıkması beklenen meşhur remdesivir ilacı nsp12 proteinini hedef alarak virüsü işlevsiz kılmayı amaçlamaktadır.

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nsp13: rna'yı düz hale getirerek okunur hale getirmek

virüs rna'sı sarmal bir biçimdedir. bu protein rna'yı düzleştirerek okunabilir ve kopyalanır hale getirdiği düşünülüyor:

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nsp14: doğrulama mekanizması 

nsp12 proteini virüsün bir kopyasını oluşturuyor ancak kopyalama sırasında bazen fazladan harfler eklenebiliyor ve bu harfler virüsün işleyini bozabiliyor. nsp14 bu gelen zinciri kontrol ediyor ve fazlalık harfleri çıkarıyor.

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nsp15: temizlik proteini

bu protein virüsün işlevlerinden sonra ortaya yayılan fazlalıkları temizliyor. bu fazlalıklara denk gelen hücre içi antiviral proteinlerin olayın farkına vararak alarm mekanizmasını çalıştırıp virüse karşı savaş açmasını engelliyor.

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nsp16: kamuflaj proteini

nsp10 ile beraber kamuflaj sağlıyor.

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s proteini: virüs dışı sivri uçlar (spike'lar)

virüs bu uçlar sayesinde hücreye tutunuyorlar. virüs resminde görünen yuvarlak yüzeyin üstündeki çiçeğimsi çıkıntılar bu proteinler. s proteini aynı zamanda virüsün dış yüzeyinde başka işlere de katılıyorlar. virüsü bu kadar tehlikeli hale getiren insan hücresine girişini çok büyük başarıyla yapması ve genel olarak s proteinine borçlu olduğu söylenebilir. virüse karşı ilaç araştırmaları s proteinlerini işlevsiz hale getirme konusunda da yoğunlaşıyorlar.

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orf3a proteini

insan hücresi virüsün attığı zokayı yutup kendi elleriyle virüsün kopyalarını oluşturduktan sonra bu virüslerin hücreyi terkederek kana tekrar karışmaları ve yeni hedef hücreler aramaları gerekiyor. orf3a proteini hem hücre duvarında delik açarak bu işi sağlıyor hem de hücre içi iltihaplanma başlatarak hücrenin dolayısıyla vücudun zarar görmesine yol açıyor.

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e- zarf proteini

bu da virüsün yağlı baloncuk çevresini oluşturan protein. membran yani m proteini ile beraber çalışıyor.

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m- membran proteini

virüsün dış yapısını oluşturan protein. içindeki rna'ları gizliyor hem de üzerindeki dikenli uçları tutuyor. e proteini ile beraber çalışıyor.

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orf6 proteini: sinyal engelleyici

insan hücresi yanlış giden bir şeyler olduğunu farkettiğinde vücudun bağışıklık sistemini harekete geçiren bir sinyal üretiyor. orf6 proteini bu sinyalin iletilmesini engelliyor.

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orf7a: kopyalanan virüsün hücreden çıkmasını sağlayan protein

insan hücresi içeride oluşan virüslerden sonra bile savaşmaktan vazgeçmiyor ve tetherin isimli bir protein yardımıyla onların hücreyi terketmesini engellemeye çalışıyor. orf7a hücrenin bu proteini salmasına engel olarak virüslerin zarar görmeden hücre dışına çıkmasına yardımcı oluyor.

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orf8: ne olduğu belli olmayan gizemli protein

bütün coronavirüs ailesine kıyasla bu virüste oldukça farklı hali bulunan bir protein. ne iş yaptığı henüz anlaşılabilmiş değil.

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n proteini: koruyucu

n proteini virüs rna'sının hücre içinde kıvrılıp dönerek sağlam ve bir arada durmasını sağlıyor.

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orf10: gizemli rna zinciri

ne iş yaptığı anlaşılamayan bir diğer bölüm. hatta bu zincir kullanılarak herhangi bir protein oluşturulduğu da kesin değil.

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kapanış zinciri: 

virüs rna'sının son bölümüne baktığımızda gördüğümüz kısım. bu zincirdeki harfleri okuyan hücre yeterli bilgiyi aldığını farkederek üretimi bitiriyor. zincirin sonu bir sürü aaaaaaaaaaaaa harflerinden oluşuyor.

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bu işlevler göze karmaşık görünse de virüsün insan eliyle üretildiği anlamına gelmiyor. insanlık daha yokken de virüsler bu şekilde çalışıyorlardı.
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kaynak: bu bilgileri bir new york times makalesinden aldım. new york times da aşağıdaki kaynaklardan almış:

fan wu et al., nature; national center for biotechnology ınformation; dr. david gordon, university of california, san francisco; dr. matthew b. frieman and dr. stuart weston, university of maryland school of medicine; dr. pleuni pennings, san francisco state university; david haussler and jason fernandes, u.c. santa cruz genomics ınstitute; journal of virology; annual review of virology.

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